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PubMedDate not supplied

[Surgery of the spleen in antiquity].

Splenic surgery, a common practice in Antiquity? Such a question will appear somewhat provocative despite an ample mention of such facts in Roman and Greek classic literature. This paper intends to explore the large border standing between myths where the spleen keeps a major place and reality which is, on this subject, far from easy to decipher. In final analysis, it seems likely that there had always existed, from the very early ages, some form of splenic cauterisation. The type of procedures reported in the texts cannot be interpreted as variant of the ritual scarifications widely practised until recently in many countries. On the other hand, the idea that physicians, at the time of Antiquity, could perform splenectomy does not seem, in spite of Ancient authors assumptions, to be considered. In fact, there is no direct testimony available on this subject in Latin or Greek medical literature. We suggest that the so-called "splenectomies" of Antiquity could have been surgical "make-believes" closely similar to the quack practices which can be yet observed in some remote countries.

Greece, Ancient↗
PubMed1984

Tumors of the appendix: II. The spectrum of carcinoid.

We reviewed the clinical data and pathologic material from 30 patients with appendiceal carcinoids. Most of the tumors were discovered incidentally in appendectomy specimens. Approximately two thirds were tiny lesions identified only by microscopic examination. One tumor metastasized to a regional lymph node. Five histologic patterns were identified. Problems in differential diagnosis may arise in interpreting the variant patterns, but these patterns appear to have no bearing on prognosis. In reviewing the literature we found that appendiceal carcinoids infrequently metastasize widely and only rarely produce the carcinoid syndrome.

Acute Disease↗
PubMedDate not supplied

[Development of an optimal scheme for calculating results of the use of an immunoenzyme test-system for determining the antigenic activity of a cultured antirabies vaccine].

Ninety-eight lots of commercial antirabies vaccine manufactured by Immunopreparat Research and Production Amalgamation have been tested using enzyme immunoassay system for the detection of rabies virus antigens. Comparison of different variants of interpreting and expressing the results helped define the optimal method for assessment of vaccine titer and reference values: optical density value equal to 0.2 is taken as the cut-off. Antigenic activity of the vaccine may be expressed in international units, similarly as immunogenic activity.

Antigens, Viral↗
PubMed1980

Anatomic variations of the carotid bifurcation affecting doppler scan interpretation.

An anatomic variant for the position of the external carotid artery (ECA) at the carotid bifurcation was noted in 5.3 percent of patients studied by Doppler ultrasound and contrast angiography. The ECA is lateral to and posterior to the internal carotid artery (ICA) in these patients. Consideration of this important variant is mandatory for accurate ultrasound image correlation.

Angiography↗
PubMed1983

[Urea (H-N) concentrations in serum and urine including determination variants].

After a concise interpretation of the urea and creatinine values a new variant of the determination of the urea concentration in the serum, the plasma, the urine and other body fluids is described. The determination is done by means of Berthelot's reaction, requires 50 microliters serum and comprehends the concentration range of 0.1 to 100 mmol/l (0.6 to 600 mg urea/100 ml). The method has a good precision, is inexpensive and renders the determination of urea possible in less than one hour.

Colorimetry↗
PubMed2025

Clinical and genetic variant re-analysis among pediatric probands undergoing genetic testing for arrhythmia syndromes.

BACKGROUND: Despite increases in genetic testing, longitudinal data regarding changes in diagnostic yield and variant reclassification for inherited arrhythmia syndromes are limited. OBJECTIVE: Determine longitudinal changes in diagnostic yield and variant classification. METHODS: Single-center retrospective study of probands <18 years undergoing genetic testing for suspected inherited cardiac conditions associated with arrhythmias, 2007 to 2018. Variants were classified as diagnostic (pathogenic/likely pathogenic), non-diagnostic (benign/likely benign [B/LB]), or variants of uncertain significance (VUS). Variant reclassification was performed in October 2023 using VarSome and American College of Medical Genetics criteria. We evaluated results by era (early 2007-2013 vs. later 2014-2018, coinciding with Sanger and next-generation sequencing, respectively) and by likelihood of disease based on clinical evaluation. RESULTS: Of 306 probands, initial testing was 23.2% diagnostic, 55.6% non-diagnostic (33.7% no variant, 21.9% B/LB), and 21.2% VUS. When comparing eras, diagnostic yield decreased (34.1%-15.3%), VUS increased (9.3%-29.9%), and non-diagnostic remained similar (55% to 57%). Variants for 22.7% (46/203) of probands with &#x2265;1 variant changed: 9.9% of diagnostic variants (7/71) downgraded to VUS or non-diagnostic, and 60.0% of VUS changed (23.1% upgraded, 36.9% downgraded). B/LB variants did not change. Probands with higher disease likelihood had 6-times the odds of diagnostic results compared to lower disease likelihood, regardless of era (odds ratio 6.3, 95% confidence interval 3.2-12.4, P < .0001). CONCLUSION: Variant reclassification led to changes in 23% of probands, both downgrading and upgrading status, even among probands initially thought to be pathogenic. When comparing later to earlier eras, VUS variants increased while diagnostic yield decreased. Findings support the need for variant re-interpretation and periodic reclassification over time.

Humans↗
PubMed2026

Somatic likelihood tiering: an interpretable post-calling triage protocol for tumor-only whole-exome variant review.

Tumor-only whole-exome sequencing (WES) is used when matched normal tissue is unavailable, but one sample can produce thousands of variants. Somatic likelihood tiering (SLT) is an interpretable post-calling protocol that ranks Mutect2 calls into four review-priority tiers using population-frequency, germline-quality, cancer-knowledge, PureCN posterior, and clonal-hematopoiesis evidence. Layer 2 distinguishes common, rare-callable, and unevaluable gnomAD states; missing or unmatchable gnomAD evidence is not positive rarity evidence. On the SEQC2 HCC1395 benchmark, the callability-aware SLT-A row contained 101 calls, 78 truth variants, 77.2% PPV (95% Wilson confidence interval 68.1%-84.3%), and a Number Needed to Review (NNR) of 1.29 (1.19-1.47). The conservative SLT-C catchment retained 352 of 455 truth variants (77.4%, 73.3%-81.0%) and all tiers together retained 430 of 455 truth variants. SNV performance is the primary calibration frame: SLT-C retained 341 of 439 SNV truth variants, whereas indel results were exploratory because only 16 truth indels were available. Clinical cohorts are reported as recall and concordance versus partially dependent matched-normal Mutect2 references, not independent clinical sensitivity. Patient-level bootstrap intervals were principal: HdM-BLCA-1 SLT-A recall was 18.2% (14.0%-23.5%), and LUAD-TW SLT-A recall was 49.1% (26.6%-63.3%) among 32 evaluable patients. The HdM-BLCA-1 median SLT-A queue remained 1277 variants per patient, so SLT reduces first-pass candidate counts but does not measure review time or eliminate FFPE candidate-count burden. SLT provides an auditable tumor-only WES review queue, not a substitute for matched-normal sequencing, independent orthogonal validation, or definitive somatic classification.

Humans↗
PubMed2000

Rare variant of the brachial artery: superficial lateral inferior type VII EAB.

This study concerns a variant of the brachial artery with a modified origin and course. The artery was studied in 418 upper limbs removed from cadavers. In one upper limb the left brachial artery bifurcated into: (1) a superficial brachial a. (the variant) crossing superficially to the bicipital aponeurosis in the cubital region and assuming the course, position, and supply area of the radial artery, and (2) the deep brachial a. (another variant). An embryologic interpretation of this anomaly is based on a variant vascular development derived from the eighth intersegmental artery. The variant is termed according to Adachi's classification schedule as arteria brachialis superficialis lateralis inferior Type VII with the addition EAB (epiaponeurosis bicipitalis, i.e., superficial to the bicipital aponeurosis). Accurate information concerning unusual patterns of the arteries in the upper limbs is clinically relevant, especially in the avoidance of accidental intra-arterial injection with reflectory vascular occlusion leading to necrosis.

Aged↗
PubMed2026

No phenotypic resistance observed for most group-3 and -4 variants in Mycobacterium tuberculosis genes related to bedaquiline, clofazimine, delamanid, and pretomanid in a Central and West African context.

The interpretation of genetic variants' association (or not) with phenotypic resistance to newly introduced and repurposed antituberculosis drugs remains challenging, as many mutations detected by whole-genome sequencing (WGS) are classified as of uncertain significance (group 3) or not associated with resistance-interim (group 4) by the World Health Organization (WHO) mutation catalog v2. We evaluated the phenotypic impact of such variants on minimum inhibitory concentrations (MICs) for bedaquiline (BDQ), clofazimine (CFZ), delamanid (DLM), and pretomanid (PA) in Mycobacterium tuberculosis complex isolates from the multi-country DIAMA cohort in sub-Saharan Africa (SSA), which recruited RR/RS-TB patients na&#xef;ve to these drugs. Among 1,475 isolates with available WGS data, 163 variants met eligibility criteria; due to viable strain unavailability, 89 isolates carrying 29 unique BDQ/CFZ-related and 60 unique DLM/PA-related variants were tested for MIC determination using broth microdilution. Additional structural modeling was performed to explore potential effects of amino-acid substitutions on protein stability. Among BDQ/CFZ-related variants, MICs above the critical concentrations (CCs) were consistently associated with mmpR5 variants, whereas variants in atpE, pepQ, and Rv1979c were not. DLM/PA variants (ddn, fbiA-D, and fgd1) were frequently detected as non-fixed populations, yet rarely yielding MIC values above the CC. Predicted structural destabilization showed no consistent association with MIC values or variant fixation status. Under the conditions tested, phenotypic resistance was not detected for most group 3 and 4 variants detected by WGS. Our data provide evidence from SSA to support improved interpretation of resistance-associated mutations for new and repurposed antituberculosis drugs.IMPORTANCEWhole-genome sequencing increasingly detects Mycobacterium tuberculosis complex mutations classified by the World Health Organization (WHO) mutation catalog v2 as group 3 variants of uncertain significance or group 4 variants not associated with resistance-interim, limiting reliable prediction of resistance to new and repurposed antituberculosis drugs. By generating minimum inhibitory concentration (MIC) data for such variants identified in a multi-country sub-Saharan African cohort, this study provides phenotypic evidence to support future refinement and expansion of the WHO mutation catalog v2. Notably, mmpR5 variants associated with elevated bedaquiline/clofazimine MICs were identified in eight isolates, suggesting that some patients in this cohort may have harbored pre-existing resistance-associated variants yet remained potentially eligible for bedaquiline-containing regimens. These findings contribute to improving the interpretation of genomic resistance data and strengthening surveillance of resistance to bedaquiline, clofazimine, delamanid, and pretomanid.

Mycobacterium tuberculosis↗
PubMed2026

Discordant neoplasms in monozygotic twins with a germline RECQL5 variant.

RECQL5 is a member of the RecQ helicase family involved in DNA replication, homologous recombination, and maintenance of genomic stability. While germline pathogenic variants in other RecQ helicases cause established cancer predisposition syndromes, the role of RECQL5 in human cancer susceptibility remains uncertain. We report monozygotic adolescent twins with distinct tumors: dysembryoplastic neuroepithelial tumor in one twin and Burkitt lymphoma in the other. Clinical genome sequencing was initially nondiagnostic, but reanalysis identified a rare heterozygous nonsense variant in RECQL5 (NM_004259.7:c.2698C>T, p.(Gln900Ter)), present in both twins and their unaffected mother. The variant is predicted to undergo nonsense-mediated mRNA decay or produce a truncated protein lacking the C-terminal SRI (Set2-Rpb1 interacting) domain, which mediates interaction with RNA polymerase II. However, tumor sequencing data were not available to evaluate loss of heterozygosity or second somatic events. Given the unaffected carrier parent, lack of tumor molecular confirmation, and the biological heterogeneity of the tumors, a causal relationship for this variant cannot be established. This case highlights the challenges of interpreting rare germline variants in genes with emerging but incompletely characterized disease associations. Although the available evidence is insufficient to establish a definitive causal relationship, the identification of a shared loss-of-function RECQL5 variant in monozygotic twins with distinct tumors is noteworthy and adds to the limited clinical evidence suggesting a potential role for RECQL5 in cancer susceptibility. Additional functional studies, tumor-based analyses and the accumulation of well-characterized clinical cases will be essential to determine whether RECQL5 contributes to hereditary cancer predisposition.

Adolescent↗
PubMed2025

HCSeeker: A classification tool for human genetic variant hot and cold spots designed for PM1 and benign criteria in the ACMG-AMP guideline.

PURPOSE: The PM1 criterion, which states that a variant is located in a mutational hot spot and/or critical and well-established functional domain without benign variation (such as the active site of an enzyme), is considered moderate evidence for assessing its pathogenicity. Although guidelines from the American College of Medical Genetics and Genomics and the Association for Molecular Pathology are widely adopted, the PM1 criterion remains limited from lacking a reliable database of variant hot spots. Compared with hot spots, cold spots are neglected by the guidelines. To improve variant classification, we suggest including cold spots for supporting benign classifications. Consequently, we have developed the HCSeeker to provide data support for PM1 and the "Benign" criteria. METHODS: HCSeeker uses the Kernel Density Estimation and the Expectation-Maximization algorithm to identify hot- and cold-spot regions. RESULTS: Through HCSeeker, we identified 988 hot spots and 682 cold spots across 889 genes and provided a public database (http://www.genemed.tech/hcseeker/) for researchers and clinicians to query variant locations, facilitating the application of American College of Medical Genetics and Genomics and the Association for Molecular Pathology PM1 or "Benign" criteria. CONCLUSION: We developed the HCSeeker tool, which can effectively identify variant hot and cold spots within genes to enhance the interpretability of gene variants.

Humans↗
PubMed2025

Identification of pathogenic variants in six Chinese families with keratoconus of autosomal dominant inheritance: pathogenicity analysis and variable phenotype.

PURPOSE: Keratoconus (KC) is a bilateral, asymmetric disease causing corneal thinning, irregular astigmatism, and vision decline, with unclear etiology. This study aims to investigate pathogenic variants of candidate genes in Chinese KC families via whole exome sequencing (WES). METHODS: The Pentacam 3D anterior segment analysis system was applied for keratectasia detection, and the Corvis ST was used for corneal biomechanics measurement. Probands from KC families were screened via WES and further verified in other family members through Sanger sequencing. Additionally, qPCR was used to validate copy number variants and identify pathogenic gene loci. The identified variants were then classified according to the Standards and Guidelines for the Interpretation of Sequence Variants published by the American College of Medical Genetics and Genomics (ACMG). Finally, STRING protein-protein interaction (PPI) networks analysis was performed to investigate interactions among candidate gene-related proteins. RESULTS: Using WES, four heterozygous missense variants were detected in the ZNF469, KRT12, COL8A2, and COL18A1 genes: c.4384G&#x2009;>&#x2009;A: p.Asp1462Asn, c.1229T&#x2009;>&#x2009;G:p.Val410Gly, c.505A&#x2009;>&#x2009;G:p.Ile169Val, and c.1159G&#x2009;>&#x2009;A:p.Gly387Arg. Additionally, a heterozygous frameshift variant was detected in the PMS2 gene: c.1551_1572del:p.Ser517Argfs*71. The affected parents carried the same variants as the probands verified by Sanger sequencing. A copy number variant was detected in the DPP6 gene: seq[GRCh38] dup(7)(q36.2q36.2) chr7:g.153782360_ 153982491dup. According to ACMG guidelines, ZNF469, KRT12, COL8A2, and COL18A1 gene variants are Likely Pathogenic; PMS2 and DPP6 gene variants are Pathogenic. STRING analysis highlights a tightly interconnected network centered on COL8A2, involving COL18A1, FN1, ZNF469, and KRT12. DPP6 was involved in KC via affecting FN1. In four of six autosomal dominant KC (adKC) families, affected parents had the same variants as probands but milder phenotypes. CONCLUSION: In this study, six novel variants in ZNF469, KRT12, COL8A2, COL18A1, PMS2, and DPP6 were linked to adKC. Family phenotypes showed variable expressivity with irregular dominance inheritance. Abnormal KC-related gene protein expression may contribute to corneal structural instability. This study broadened KC genetic screening candidates and suggested genetic testing could aid early KC diagnosis and intervention.

Adult↗
PubMed2002

[Transient improvement of writing tremor by holding breath in volition: a case report].

We report a 76-year-old Japanese woman who had tremor of her hand during writing. Her past and family histories were unremarkable. On neurological examination, there was no abnormal finding except the writing tremor and the postural tremor of her lips and jaw. Surface EMG studies revealed that regular grouped discharges, at a frequency of about 5 Hz, appeared in the wrist flexor and extensor muscles soon after she start writing; these grouped discharges were inhibited while holding breath. Her postural tremor improved after consumption of a small amount of alcohol, suggesting that she had essential tremor. Thus, she may be diagnosed as having a variant of essential tremor. On the other hand, this tremor may be interpreted as a variant of writer's cramp, since her writing tremor transiently improved when she hold breath, just like a trick. In patients with dystonia, it is well known that dystonic symptoms can be temporally ameliorated by geste movement like a "trick". Although the pathophysiological relationship between primary writing tremor and writer's cramp are unclear, the unique characters of this tremor may suggest that a focal task-specific tremor and essential tremor can co-exist.

Aged↗