bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impact of thymosin α1 as an immunomodulatory therapy on long-term survival of non-small cell lung cancer patients after R0 resection: a propensity score-matched analysis
Authors: Guo Cheng-Lin , Mei Jian-Dong , Jia Yu-Long , Gan Fan-Yi , Tang Yu-Dong , Liu Cheng-Wu , Zeng Zhen , Yang Zhen-Yu , Deng Sen-Yi , Sun Xing , Liu Lun-Xu 
Published: November 2021

Abstract

Background:
There is limited information about thymosin α1 (Tα1) as adjuvant immunomodulatory therapy, either used alone or combined with other treatments, in patients with non-small cell lung cancer (NSCLC). This study aimed to evaluate the effect of adjuvant Tα1 treatment on long-term survival in margin-free (R0)-resected stage IA–IIIA NSCLC patients.

Methods:
A total of 5746 patients with pathologic stage IA-IIIA NSCLC who underwent R0 resection were included. The patients were divided into the Tα1 group and the control group according to whether they received Tα1 or not. A propensity score matching (PSM) analysis was performed to reduce bias, resulting in 1027 pairs of patients.

Results:
After PSM, the baseline clinicopathological characteristics were similar between the two groups. The 5-year disease-free survival (DFS) and overall survival (OS) rates were significantly higher in the Tα1 group compared with the control group. The multivariable analysis showed that Tα1 treatment was independently associated with an improved prognosis. A longer duration of Tα1 treatment was associated with improved OS and DFS. The subgroup analyses showed that Tα1 therapy could improve the DFS and/or OS in all subgroups of age, sex, Charlson Comorbidity Index (CCI), smoking status, and pathological tumor-node-metastasis (TNM) stage, especially for patients with non-squamous cell NSCLC and without targeted therapy.

Conclusion:
Tα1 as adjuvant immunomodulatory therapy can significantly improve DFS and OS in patients with NSCLC after R0 resection, except for patients with squamous cell carcinoma and those receiving targeted therapy. The duration of Tα1 treatment is recommended to be >24 months.
Blast Injury to the Hand: Assessing the Injury Pattern and Functional Outcome of the Thumb
Authors: Rivedal David D. , Coon Christopher , Sanger James R. , Hettinger Patrick 
Published: November 2021

Background:
In the United States, approximately 30% of about 10,000 annual blast injuries involve the hand, causing a broad spectrum of injury severity. The first web space is typically most severely affected. As the carpometacarpal (CMC) joint is critical to the unique function of the thumb, we evaluated typical patterns of injury to this joint, subsequent salvageability and functional outcomes of the thumb.

Methods:
We conducted a retrospective chart review on patients with blast injuries to the hand from January 1995 through July 2019 and excluded penetrating trauma. We assessed hand function as reported in occupational therapy records. Injury severity was classified independently by structures.

Results:
Twenty-one patients were included, two with bilateral injuries, for a total of 23 hands. Eighteen patients had injuries to one or both thumbs, for a total of 20 thumbs evaluated. Average follow-up was 1.58 years. Most injuries qualified as severe in at least one category: soft tissue, neurovascular, or bone/joint. All 10 CMC joint dislocations required surgical fixation and pinning. Eight patients had applicable occupational therapy notes available. Severely injured thumbs had statistically significant decreased range of motion (ROM) at the interphalangeal joint, metacarpophalangeal joint and with radial abduction compared to mildly injury thumbs (P value 0.02, 0.03, 0.04, respectively).

Conclusions:
Blast injury to the hand often results in severe deficits, frequently affecting thumb functionality and irreversibly altering occupational capabilities. Half the patients studied had severe damage to the thumb CMC joint. Objectively, severely injured thumbs had significantly worse ROM than mildly injured thumbs.
Less-invasive Treatment for Group A Streptococcal Fasciitis with Rapid Antigen Detection Test and Collagen/Gelatin Sponge
Authors: Tsuge Itaru , Matsui Miho , Takeda Takuma , Yamanaka Hiroki , Katsube Motoki , Sakamoto Michiharu , Morimoto Naoki 
Published: November 2021

Summary:
Patients with severe group A Streptococcus (GAS) induced necrotizing soft tissue infection sometimes develop Streptococcal toxic shock syndrome, which is a life-threatening condition with an extremely high fatality rate. Obtaining survival is the most important goal; however, an early diagnosis for debridement surgery and quick granulation formation for skin grafting surgery can better preserve the extremity functions. The patient was a 47-year-old man with a history of atopic dermatitis who presented with GAS-induced necrotizing soft tissue infection in his left lower extremity. His vital signs indicated shock, and he was diagnosed with streptococcal toxic shock syndrome. Emergency surgery was performed with his body pressure maintained with noradrenaline. Intraoperatively, rapid antigen detection tests (RADTs) were negative in the medial thigh and positive in the lower leg, which helped in decision-making regarding the area of aggressive debridement surgery. The wound culture results matched the intraoperative rapid antigen detection test results. A collagen/gelatin sponge with the sustained release of basic fibroblast growth factor was used as an artificial dermis before skin grafting. Excellent granulation was obtained, and skin grafting surgery was performed on the 11th day after collagen/gelatin sponge placement. He was discharged home on the 42nd day with normal lower extremity functions. First, an intraoperative diagnosis using GAS-rapid antigen detection tests with an appropriate sampling method from small incisions avoided excessive surgical debridement. Second, collagen/gelatin sponge with the sustained release of basic fibroblast growth factor promoted quick granulation tissue formation for wound bed preparation. These efforts resulted in the successful less-invasive treatment of a patient with streptococcal toxic shock syndrome caused by GAS-induced necrotizing soft tissue infection.
Research Productivity among Plastic Surgeons in the State of Israel: h-index and M-quotient Assessment
Authors: Har-Shai Lior , Ofek Sar-El , Lavi Idit , Cohen Keren H. , Cohen Avi A. , Ad-El Dean D. , Shay Tamir 
Published: November 2021

Background:
The h-index has been proven in the US and Canada to be a solid tool to assess the quality and impact of individual scientific work in the field of plastic surgery. M-quotient is an additional metric that mitigates the h-index’s inherent bias toward more seasoned researchers. The objective of this study was evaluating the relationship between h-index and M-quotient and research productivity among plastic surgeons in the state of Israel.

Methods:
A list of all Israeli board-certified plastic surgeons registered in the Israeli Society of Plastic and Aesthetic Surgery was obtained from the organization’s website. Relevant demographic and academic factors of each surgeon were retrieved. The Scopus database was queried to determine each surgeon’s h-index and M-quotient, among other bibliometric parameters.

Results:
Our study included 173 plastic surgeons, 90% of whom were men. In total, 49.7% were working in academically affiliated hospitals; 14.4% of the surgeons had an academic rank. The mean h-index was 6.13; mean M-quotient was 0.27. Statistical analysis demonstrated a positive correlation between total number of publications (P < 0.0001), total number of citations (P < 0.0001), the surgeon’s seniority (P < 0.0001), academic rank (P = 0.007), appointed as past/present plastic surgery department director (P < 0.0001), and working in an academic affiliated hospital (P < 0.025). The same parameters were found to have a positive correlation with M-quotient.

Conclusions:
The h-index is an effective measure to compare plastic surgeons’ research productivity in Israel. M-quotient is an ancillary tool for the assessment of research productivity among plastic surgeons, with the advent of neutralizing the surgeon’s seniority.
Corneal Endothelial Cell Loss After Endocapsular and Supracapsular Phacoemulsification: The PERCEPOLIS Randomized Clinical Trial
Authors: Perone Jean-Marc , Ghetemme Cedric , Zevering Yinka , Zaidi Mohamed , Ouamara Nadia , Goetz Christophe , Lhuillier Louis 
Published: November 2021

Purpose:
Subluxation techniques are superior to divide-and-conquer in procedure duration, pain, and ultrasound quantity, but their safety in endothelial cell loss (ECL) is unclear. This randomized single-blind noninferiority clinical trial aimed to determine whether subluxation supracapsular phacoemulsification techniques are inferior to a reference endocapsular technique (divide-and-conquer) regarding postoperative corneal ECL.

Methods:
Patients (aged18 years or older) with greater than +0.2 logarithm of the minimum angle of resolution best spectacle–corrected visual acuity and normal to severe density cataract were randomized to subluxation or divide-and-conquer phacoemulsification in 2015 to 2016. Follow-up with ophthalmic tests was conducted on day 4 and months 1, 3, and 12. The primary study outcome was ECL at all time points. Secondary study end points were operative variables, including effective phaco time and procedure duration. A clinically relevant noninferiority ECL limit was established on the basis of the literature.

Results:
In total, 292 patients (mean age, 73 yrs; 59% female) were randomized and underwent subluxation (n = 148) or divide-and-conquer (n = 144). Day 4 and month 1, 3, and 12 data were available for 243, 270, 275, and 198 patients, respectively. The unexpectedly high dropout at 12 months meant that the 12-month ECL data could only be assessed qualitatively. Surgery was successful in all patients. Subluxation was noninferior to divide-and-conquer in ECL. Effective phaco times were similar, but subluxation associated with shorter procedure duration.

Conclusions:
The subluxation technique was noninferior to divide-and-conquer regarding postoperative ECL, at least in the first 3 months, and associated with reduced intervention time. Subluxation techniques may be suitable alternatives to endocapsular techniques.

Clinical Trial Registration
—URL: ClinicalTrials.gov. Unique identifier: NCT02535819.
Mechanical Thrombectomy Outcomes in COVID-19 Patients With Acute Ischemic Stroke
Authors: Zureigat Hadil , Alhusban Muna , Cobia Miles 
Published: November 2021

Background:
Coronavirus disease 2019 (COVID-19) has been shown to associate with increased risk of thromboembolic events. Mechanical thrombectomy (MT) has long been used to effectively manage those with large-vessel occlusive (LVO) stroke and has similarly been implemented in the management of stroke in COVID-19 patients.

Review Summary:
The COVID-19 pandemic took the health care sector by a storm. Thus, less is known about MT outcomes in this population and evidence suggesting poor outcomes postthrombectomy for COVID-19 patients is accumulating. We provide a narrative on some of the published studies on the outcomes of MT in COVID-19 patients with LVO between March 2020 and February 2021. A description of patient characteristics, risk factors, COVID-19 infection severity, stroke features and thrombectomy success in this population is also presented as data from several studies show that LVO in COVID-19 patients may have some distinguishing characteristics that make management more challenging.

Conclusions:
The effect of COVID-19 on the long-term prognosis of stroke patients after thrombectomy is yet to be determined. The accumulating evidence from current studies indicates a negative impact of COVID-19 on outcomes in acute ischemic stroke patients who receive MT, irrespective of timely, successful angiographic recanalization. This review may help alert clinicians of some of the COVID-19-specific postthrombectomy challenges.
Diagnostic Accuracy of Dried Plasma Spot Specimens for HIV-1 Viral Load Testing: A Systematic Review and Meta-analysis
Authors: Fong Youyi , Markby Jessica , Andreotti Mauro , Beck Ingrid , Bourlet Thomas , Brambilla Don , Frenkel Lisa , Lira Rosalia , Nelson Julie A. E. , Pollakis Georgios , Reigadas Sandrine , Richman Douglas , Sawadogo Souleymane , Waters Laura , Yang Chunfu , Zeh Clement , Doherty Meg , Vojnov Lara 
Published: November 2021

Background:
Dried plasma spot specimens may be a viable alternative to traditional liquid plasma in field settings, but the diagnostic accuracy is not well understood.

Methods:
Standard databases (PubMed and Medline), conferences, and gray literature were searched until January 2019. The quality of evidence was evaluated using the Standards for Reporting Studies of Diagnostic Accuracy and Quality Assessment of Diagnostic Accuracy Studies-2 criteria. We used univariate and bivariate random effects models to determine misclassification, sensitivity, and specificity across multiple thresholds, overall and for each viral load technology, and to account for between-study variation.

Results:
We identified 23 studies for inclusion in the systematic review that compared the diagnostic accuracy of dried plasma spots with that of plasma. Primary data from 16 of the 23 studies were shared and included in the meta-analysis, representing 18 countries, totaling 1847 paired dried plasma spot:plasma data points. The mean bias of dried plasma spot specimens compared with that of plasma was 0.28 log10 copies/mL, whereas the difference in median viral load was 2.25 log10 copies/mL. More dried plasma spot values were undetectable compared with plasma values (43.6% vs. 29.8%). Analyzing all technologies together, the sensitivity and specificity of dried plasma spot specimens were >92% across all treatment failure thresholds compared and total misclassification <5.4% across all treatment failure thresholds compared. Some technologies had lower sensitivity or specificity; however, the results were typically consistent across treatment failure thresholds.

Discussion:
Overall, dried plasma spot specimens performed relatively well compared with plasma with sensitivity and specificity values greater than 90% and misclassification rates less than 10% across all treatment failure thresholds reviewed.
Pharmacokinetics of Atazanavir Boosted With Cobicistat in Pregnant and Postpartum Women With HIV
Authors: Momper Jeremiah D. , Wang Jiajia , Stek Alice , Shapiro David E. , Powis Kathleen M. , Paul Mary E. , Badell Martina L. , Browning Renee , Chakhtoura Nahida , Denson Kayla , Rungruengthanakit Kittipong , George Kathleen , Capparelli Edmund V. , Mirochnick Mark , Best Brookie M. ,   for the IMPAACT P1026s Protocol Team
Published: November 2021

Background:
This study evaluated atazanavir and cobicistat pharmacokinetics during pregnancy compared with postpartum and in infant washout samples.

Setting:
A nonrandomized, open-label, parallel-group, multicenter prospective study of atazanavir and cobicistat pharmacokinetics in pregnant women with HIV and their children.

Methods:
Intensive steady-state 24-hour pharmacokinetic profiles were performed after administration of 300 mg of atazanavir and 150 mg of cobicistat orally in fixed-dose combination once daily during the second trimester, third trimester, and postpartum. Infant washout samples were collected after birth. Atazanavir and cobicistat were measured in plasma by validated high-performance liquid chromatography-ultraviolet and liquid chromatography-tandem mass spectrometry assays, respectively. A 2-tailed Wilcoxon signed-rank test (α = 0.10) was used for paired within-participant comparisons.

Results:
A total of 11 pregnant women enrolled in the study. Compared with paired postpartum data, atazanavir AUC0
–24 was 26% lower in the second trimester [n = 5, P = 0.1875, geometric mean of ratio (GMR) = 0.739, 90% CI: 0.527 to 1.035] and 54% lower in the third trimester (n = 6, GMR = 0.459, P = 0.1563, 90% CI: 0.190 to 1.109), whereas cobicistat AUC0-24 was 35% lower in the second trimester (n = 5, P = 0.0625, GMR = 0.650, 90% CI: 0.493 to 0.858) and 52% lower in the third trimester (n = 7, P = 0.0156, GMR = 0.480, 90% CI: 0.299 to 0.772). The median (interquartile range) 24-hour atazanavir trough concentration was 0.21 μg/mL (0.16–0.28) in the second trimester, 0.21 μg/mL (0.11–0.56) in the third trimester, and 0.61 μg/mL (0.42–1.03) in postpartum. Placental transfer of atazanavir and cobicistat was limited.

Conclusions:
Standard atazanavir/cobicistat dosing during pregnancy results in lower exposure which may increase the risk of virologic failure and perinatal transmission.
Simulated attack reveals how lesions affect network properties in post-stroke aphasia
Authors: Medaglia John D. , Erickson Brian A. , Pustina Dorian , Kelkar Apoorva S. , DeMarco Andrew T. , Dickens J. Vivian , Turkeltaub Peter E. 
Published: November 2021

AbstractAphasia is one of the most prevalent cognitive syndromes caused by stroke. The rarity of premorbid imaging and heterogeneity of lesion size and extent obfuscates the links between the local effects of the lesion, global anatomical network organization, and aphasia symptoms. We applied a simulated attack approach to examine the effects of 39 stroke lesions on network topology by simulating their effects in a control sample of 36 healthy brain networks. We focused on measures of global network organization thought to support overall brain function and resilience in the whole brain and within the left hemisphere. After removing lesion volume from the network topology measures and behavioral scores (the Western Aphasia Battery Aphasia Quotient; WAB-AQ), four behavioral factor scores obtained from a neuropsychological battery, and a factor sum), we compared the behavioral variance accounted for by simulated post-stroke connectomes to that observed in the randomly permuted data. Overall, global measures of network topology in the whole brain and left hemisphere accounted for 10% variance or more of the WAB-AQ and the lexical factor score beyond lesion volume and null permutations. Streamline networks provided more reliable point estimates than FA networks. Edge weights and network efficiency were weighted most highly in predicting the WAB-AQ for FA networks. Overall, our results suggest that global network measures can provide modest statistical value predicting overall aphasia severity, but less value in predicting specific behaviors. Variability in estimates could be induced by premorbid ability, deafferentation and diaschisis, and neuroplasticity following stroke.
Massively parallel identification of functionally consequential noncoding genetic variants in undiagnosed rare disease patients
Authors: McQuerry Jasmine A. , Mclaird Merry , Hartin Samantha N. , Means John C. , Johnston Jeffrey , Pastinen Tomi , Younger Scott T. 
Published: November 2021

AbstractClinical whole genome sequencing has enabled the discovery of potentially pathogenic noncoding variants in the genomes of rare disease patients with a prior history of negative genetic testing. However, interpreting the functional consequences of noncoding variants and distinguishing those that contribute to disease etiology remains a challenge. Here we address this challenge by experimentally profiling the functional consequences of rare noncoding variants detected in a cohort of undiagnosed rare disease patients at scale using a massively parallel reporter assay. We demonstrate that this approach successfully identifies rare noncoding variants that alter the regulatory capacity of genomic sequences. In addition, we describe an integrative analysis that utilizes genomic features alongside patient clinical data to further prioritize candidate variants with an increased likelihood of pathogenicity. This work represents an important step towards establishing a framework for the functional interpretation of clinically detected noncoding variants.
A Comprehensive In Silico Study for the Identification of Therapeutic Target Against Peripheral Neuropathic Pain in humans
Authors: Bhowmik Sagar , Samrat Sheikh Mohiuddin , Paul Debneela 
Published: November 2021

AbstractBackgroundVGF (non-acronymic) is a neuropeptide precursor or neuro-protein or neurosecretory protein which plays vital roles in the regulation of gastric contractility, mood regulation, and peripheral neuropathic pain and possibly, cancer.ObjectiveVGF may be a potential target as it has a unique contribution to the development of neuropathic pain which is a target for Oxymatrine (OMTR).MethodBased on this, we have endeavored to discover VGF inhibitors from the ChEMBL database of Oxymatrine (OMTR) analogues by employing homology modelling, molecular docking and pharmacophore analysis.ResultOur in silico investigation reveals that 13-Methoxymatrine has desired characteristics for becoming a future formulation.ConclusionTo confirm the efficacy of this compound, essential animal and clinical trials are needed to be performed. We believe that our present study will help to find an efficient and effective therapy for treating neuropathic pain in human which is modulated by VGF.
Protein loop modeling and refinement using deep learning models
Authors: Pan Feng , Zhang Yuan , Lo Chun-Chao , Mandal Arunima , Liu Xiuwen , Zhang Jinfeng 
Published: November 2021

AbstractLoops in proteins play essential roles in protein functions and interactions. The structural characterization of loops is challenging because of their conformational flexibility and relatively poor conservation in multiple sequence alignments. Many experimental and computational approaches have been carried out during the last few decades for loop modeling. Although the latest AlphaFold2 achieved remarkable performance in protein structure predictions, the accuracy of loop regions for many proteins still needs to be improved for downstream applications such as protein function prediction and structure based drug design. In this paper, we proposed two novel deep learning architectures for loop modeling: one uses a combined convolutional neural network (CNN)-recursive neural network (RNN) structure (DeepMUSICS) and the other is based on refinement of histograms using a 2D CNN architecture (DeepHisto). In each of the methods, two types of models, conformation sampling model and energy scoring model, were trained and applied in the loop folding process. Both methods achieved promising results and worth further investigations. Since multiple sequence alignments (MSA) were not used in our architecture, the energy scoring models have less bias from MSA. We believe the methods may serve as good complements for refining AlphaFold2 predicted structures.
Metabolic heritage mapping: heterogenous pools of cytoplasmic nucleotide sugars are selectively utilized by various glycosyltransferases
Authors: Sosicka Paulina , Ng Bobby G. , Pepi Lauren E. , Shajahan Asif , Wong Maurice , Scott David A. , Matsumoto Kenjiroo , Xia Zhi-Jie , Lebrilla Carlito B. , Haltiwanger Robert S. , Azadi Parastoo , Freeze Hudson H. 
Published: November 2021

ABSTRACTBiosynthesis of macromolecules requires precursors such as sugars or amino acids, originating from exogenous/dietary sources, reutilization/salvage of degraded molecules or de novo synthesis. Since these sources are assumed to contribute to one homogenous pool, their individual contributions are often overlooked. Protein glycosylation uses monosaccharides from all the above sources to produce nucleotide sugars required to assemble hundreds of distinct glycans. Here we demonstrate that cells identify the origin/heritage of the monosaccharide, fucose, for glycosylation. We measured the contribution of GDP-fucose from each of these sources for glycan synthesis and found that different fucosyltransferases, individual glycoproteins, and linkage-specific fucose residues identify and select different GDP-fucose pools dependent on their heritage. This supports the hypothesis that GDP-fucose exists in multiple, distinct pools, not as a single homogenous pool. The selection is tightly regulated since the overall pool size remains constant. We present novel perspectives on monosaccharide metabolism, which may have general applicability.