bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Telemedicine Alternative to the 6-Minute Walk Test Using Personal Activity Trackers in Liver Transplant Candidates
Authors: Duarte-Rojo Andres , Brown Rebecca A. , Bloomer Pamela M. , Nunez Duarte Marie , Grubbs Rachel K. , Hernaez Ruben 
Published: July 2022

Background.
The COVID-19 pandemic has limited liver transplant (LT) candidates access to clinics. Telehealth methods to assess frailty are needed. We developed a method to estimate the step length of LT candidates, which would permit remotely obtaining the 6-min walk test (6MWT) distance with a personal activity tracker (PAT).

Methods.
6MWT was performed while candidates wore a PAT. On first 21 subjects (stride cohort), the step length was measured and compared with calculated one (6MWT-distance/6MWT steps). On a second cohort (PAT-6MWT; n = 116), we collected the 6MWT step count and used multivariable models to generate formulas estimating step length. We multiplied the estimated step length times 6MWT steps to estimate the distance and compared it to the measured distance. The liver frailty index (LFI) and 6MWT were used as frailty metrics.

Results.
Measured/calculated step length were highly correlated (ρ = 0.85; P < 0.001) in the stride cohort. In the PAT-6MWT cohort, LFI was the strongest variable associated with step length, along with height, albumin, and large-volume paracentesis (R
2 = 0.58). On a second model without LFI, age, height, albumin, hemoglobin, and large-volume paracentesis were strongly associated with step length (R
2 = 0.45). There was a robust correlation between observed 6MWT and PAT-6MWT utilizing step length equations with (ρ = 0.80; P < 0.001) or without LFI (ρ = 0.75; P < 0.001). Frailty by 6MWT <250 m did not change significantly using the observed (16%) or the with/without LFI-estimated (14%/12%) methods.

Conclusions.
We created a method to obtain 6MWT distance remotely with the use of a PAT. This novel approach opens the possibility of performing telemedicine PAT-6MWT to monitor LT candidates’ frailty status.
Alterations in Somatic Driver Genes Are Associated with Response to Neoadjuvant FOLFIRINOX in Patients with Localized Pancreatic Ductal Adenocarcinoma
Authors: Ecker Brett L , Court Colin M , Janssen Quisette P , Tao Alice J , D’Angelica Michael I , Drebin Jeffrey A , Gonen Mithat , O’Reilly Eileen M , Jarnagin William R , Wei Alice C ,   for the David M Rubenstein Center for Pancreatic Cancer Research Group at Memorial Sloan Kettering Cancer Center
Published: July 2022

BACKGROUND:
There is increased use of neoadjuvant fluorouracil, leucovorin, irinotecan, and oxaliplatin (FOLFIRINOX) in the management of localized pancreatic ductal adenocarcinoma (PDAC), yet there are few validated biomarkers of treatment response.

STUDY DESIGN:
Consecutive patients (n = 196) with resectable, borderline resectable or locally advanced PDAC (2012–2019) receiving FOLFIRINOX as initial treatment and with targeted sequencing of a pretreatment biopsy were identified in a prospective institutional database. Genomic alterations were determined in the 4 driver mutations (KRAS, TP53, CDKN2A, SMAD4), and associations between genomic alterations and clinical outcomes were assessed.

RESULTS:
Alterations in KRAS (n = 172, 87.8%) and TP53 (n = 131, 66.8%) were common; alterations in CDKN2A (n = 49, 25.0%) and SMAD4 (n = 36, 18.4%) were less frequently observed. A total of 105 patients (53.6%) were able to undergo resection, of whom 8 (7.6%) had a complete/near-complete pathologic response. There were no somatic alterations associated with major pathologic response. Alterations in SMAD4 were associated with a lower rate of surgical resection (27.8% vs 59.4%, p < 0.001); this was additionally observed in a multivariable regression model accounting for resectability status (OR 0.35, 95% confidence interval [CI] 0.15–0.85). Thirty-three patients (16.8%) developed metastatic disease while on neoadjuvant therapy. SMAD4 alterations were associated with a significant risk of metastatic progression on therapy when controlling for resectability status (OR 3.31, 95% CI 1.44–7.60).

CONCLUSIONS:

SMAD4 alterations are associated with more frequent development of metastasis during neoadjuvant FOLFIRINOX and lower probability of reaching surgical resection. Evaluation of alternative chemotherapy regimens in patients with SMAD4 alterations will be important to distinguish whether this represents a prognostic or predictive biomarker.
Robotic Foregut Surgery in the Veterans Health Administration: Increasing Prevalence, Decreasing Operative Time, and Improving Outcomes
Authors: Napolitano Michael A , Zebley James A , Wagner Kelly , Holleran Timothy J , Werba Gregor , Sparks Andrew D , Trachiotis Gregory , Brody Fred 
Published: July 2022

BACKGROUND:
Historically, robotic surgery incurs longer operative times, higher costs, and nonsuperior outcomes compared with laparoscopic surgery. However, in areas of limited visibility and decreased accessibility such as the gastroesophageal junction, robotic platforms may improve visualization and facilitate dissection. This study compares 30-day outcomes between robotic-assisted foregut surgery (RAF) and laparoscopic-assisted foregut surgery in the Veterans Health Administration.

STUDY DESIGN:
This is a retrospective review of the Veterans Affairs Quality Improvement Program database. Patients undergoing laparoscopic-assisted foregut surgery and RAF were identified using CPT codes 43280, 43281, 43282, and robotic modifier S2900. Multivariable logistic regression and multivariable generalized linear models were used to analyze the independent association between surgical approach and outcomes of interest.

RESULTS:
A total of 9,355 veterans underwent minimally invasive fundoplication from 2008 to 2019. RAF was used in 5,392 cases (57.6%): 1.63% of cases in 2008 to 83.41% of cases in 2019. After adjusting for confounding covariates, relative to laparoscopic-assisted foregut surgery, RAF was significantly associated with decreased adjusted odds of pulmonary complications (adjusted odds ratio [aOR] 0.44, p < 0.001), acute renal failure (aOR 0.14, p = 0.046), venous thromboembolism (aOR 0.44, p = 0.009) and increased odds of infectious complications (aOR 1.60, p = 0.017). RAF was associated with an adjusted mean ± SD of 29 ± 2–minute shorter operative time (332 minutes vs 361 minutes; p < 0.001).

CONCLUSIONS:
Veterans undergoing RAF ascertained shorter operative times and reduced complications vs laparoscopy. As surgeons use the robotic platform, clinical outcomes and operative times continue to improve, particularly in operations where extra articulation in confined spaces is required
Women Empowering Women: Assessing the American College of Surgeons Women in Surgery Committee Mentorship Program
Authors: Oppenheimer-Velez Marianna , Sims Carrie , Labiner Hanna , Baxter Nancy , Kozar Rosemary , McCoy Jacee , Sanfey Hilary , Litle Virginia , Klingensmith Mary , Pories Susan 
Published: July 2022

BACKGROUND:
Mentorship is an important factor for career promotion and professional development. The Women in Surgery Committee developed a mentorship program that matched early career female surgeons to senior female surgeons for 1 year. We hypothesized participation in the program would empower junior surgeons by providing opportunities to network and hone skills necessary to attain their career goals.

METHODS:
Survey was sent 4 to 6 weeks after program completion. Statements about mentorship and value of the Women in Surgery Committee program were ranked on a 5-point Likert scale ranging from strongly disagree (1) to strongly agree (5). Participants were compared based on frequency of encounters using Student’s t-test.

RESULTS:
A total of 105 pairs were identified; response rate was 60%. Results reported as (mean ± SD). Participants believed mentorship was essential for young surgeons (4.5 ± 1.0), and limiting the program to female surgeons added value (4.4 ± 0.6). When compared with mentees who met less than 4 times in a year, those who met 4 or more times perceived the program as beneficial (4.4 ± 0.82, p < 0.001). Mentees who met 4 or more times in a year benefitted from creating and achieving goals (4.3 ± 0.75, p < 0.001), setting expectations (4.5 ± 0.6, p < 0.001), providing networking opportunities (4.1 ± 1.1, p < 0.05), and developing professional skills (3.9 ± 0.98).

Conclusion:
The Women in Surgery Committee Mentorship Program provides an opportunity for young female surgeons; however, perceived benefit is dependent on mentee engagement.
Chromosome 2q12.3-q13 copy number variants in patients with neurodevelopmental disorders: genotype-phenotype correlation and new hotspots
Authors: Aarabi Mahmoud , Baumann Jacqueline , Babcock Melanie , Kessler Elena , Sebastian Jessica , Madan-Khetarpal Suneeta , Hu Jie , Ou Zhishuo , Yatsenko Svetlana 
Published: July 2022

Introduction
The complex structure of the chromosome 2q12.3-q13 region provides a high chance of recombination events between various low copy repeats (LCRs). Copy number variants (CNV) in this region are present in both healthy populations and individuals affected with developmental delay, autism and congenital anomalies. Variable expressivity, reduced penetrance and limited characterization of the affected genes have complicated the classification of the CNVs clinical significance.

Methods
Chromosomal microarray analysis data were reviewed for 10 298 patients with neurodevelopmental disorders referred to the UPMC Medical Genetics and Genomics Laboratories. A genotype-phenotype correlation was performed among the patients harboring the 2q12.3-q13 CNVs with overlapping genomic intervals.

Results
We identified 17 (1 in ~600) individuals with rare CNVs in the 2q12.3-q13 region, including nine patients with deletions, seven individuals with duplications and one patient who had both a deletion and a duplication. Likely pathogenic CNVs with the breakpoints between LCRs encompassing the potential dosage-sensitive genes BCL2L11, BUB1, FBLN7 and TMEM87B were the most common. CNVs were also observed between LCRs surrounding the RANBP2 and LIMS1 genes.

Conclusion:
Our study provides evidence for pathogenic CNV hotspots within the chromosome 2q12.3-q13 region. We suggest CNV classification based on the affected interval and the involvement of potential dosage-sensitive genes in these patients.
Vaccine, Booster and Natural Antibody Binding to SARS-CoV-2 Omicron (BA.1) Spike Protein and Vaccine Efficacy
Authors: James-Pemberton Philip H. , Helliwell Mark W. , Olkhov Rouslan V. , Kohli Shivali , Westlake Aaron C. , Farrar Benjamin M. , Sutton Ben J. , Ager Nicholas D. , Shaw Andrew M. 
Published: July 2022

AbstractThe SARS-CoV-2 Omicron variant (BA.1) has 25 unique mutations to the Spike glycoprotein, suggesting the efficacy of current vaccines against the new variant may be seriously degraded. A fully quantitative antibody binding study was performed for Spike Omicron (SO) and original Spike (S) proteins simultaneously on three cohorts of patients: convalescent following RT-PCR-confirmed infection in early 2020, double-vaccinated at ≥2 weeks, and vaccine boosters. The average (mode) of the booster cohort response distributions were 15.1 mg/L and 13.4 mg/L for S and SO, respectively, compared with the significantly lower double-vaccinated average, S=2.4 mg/L, SO=2.0 mg/L, and natural infections average S=2.0 mg/L, SO = 1.8 mg/L. A preliminary epitope degradation screen was performed for a panel of antibodies raised to the S1 and S2 regions of the original S protein. The panel showed significant degradation to antibody epitopes in the S1 region. Differential antibody binding of the vaccine response to S and SO suggests vaccine efficacy may be reduced by up to 50% against the Omicron variant.
A Multimodal Assessment of the Heterogeneous Nature of Post-mTBI Dizziness
Authors: Pelo Ryan , Gaudette Elle , Millsap Leah , Martindale Cecilia , Dibble Leland E. , Cortez Melissa M. , Fino Peter C. 
Published: July 2022

ABSTRACTDizziness after mild traumatic brain injury (mTBI) is commonly attributed to impairment within the vestibular system. However, oculomotor, mobility, and autonomic dysfunction can also contribute to patient-reported dizziness. The purpose of this preliminary study was to examine whether a multimodal battery of assessments could help explain patient-reported dizziness after mTBI. Twenty-three participants with concussion-related symptoms completed the Dizziness Handicap Inventory (DHI) to evaluate burden imposed by dizziness on daily activities and a battery of tests designed to incorporate domains that have been shown to contribute to dizziness (e.g., vestibular, oculomotor, balance and mobility, and autonomic dysfunction). Specific outcomes included quantitative variables obtained from: Vestibular Ocular Motor Screening (VOMS); standing for 30 seconds with feet together, eyes closed, with hands on their hips on both firm and foam surfaces; walking for one minute at a comfortable pace; and a Head-up Tilt (HUT) Test. Univariate associations between DHI and individual measures were assessed, and a backwards-stepwise regression model determined the multi-variable association. There were no strong associations and only a few moderate associations between individual functional measure and DHI total score. A total of eight variables had univariate correlation coefficients larger than 0.20 in magnitude. The final model from the backwards-stepwise procedure explained 69% of the variance in DHI and retained only three variables: peak turning speed from the one-minute walk; mean blood pressure (MBP) during the HUT; and the total VOMS score. Isolated assessments of individual domains of function have weak-to-moderate associations with post-mTBI dizziness. Conversely, a multivariable model that contained measures of mobility, autonomic function, and symptomatic complaints to vestibular and ocular provocation explained 69% of the variance in dizziness. These results suggest that dizziness is physiologically heterogeneous in nature and support the use of multi-domain assessments in patients with dizziness after mTBI.
Thiol-mediated Uptake of a Cysteine-containing Nanobody for Anti-Cancer Drug Delivery
Authors: Goerdeler Felix , Reuber Emelie E. , Lühle Jost , Leichnitz Sabrina , Freitag Anika , Nedielkov Ruslan , Möller Heiko M. , Seeberger Peter H. , Moscovitz Oren 
Published: July 2022

AbstractThe identification of tumor-specific biomarkers is one of the bottlenecks in the development of cancer therapies. Previous work revealed altered surface levels of reduced/oxidized cysteines in many cancers due to overexpression of redox-controlling proteins such as protein disulfide isomerases on the cell surface. Alterations in surface thiols can promote cell adhesion and metastasis, making thiols attractive targets for treatment. Only a few tools are available to study surface thiols on cancer cells and exploit them for theranostics. Here, we describe a nanobody (CB2) that recognizes B cell lymphoma in a thiol-dependent manner. CB2 binding strictly requires the presence of a non-conserved cysteine in the antigen-binding region and correlates with elevated surface levels of free thiols on B cell lymphoma compared to healthy lymphocytes. Nanobody CB2 can induce complement-dependent cytotoxicity against lymphoma cells when functionalized with synthetic rhamnose trimers. Lymphoma cells internalize CB2 in a thiol-mediated manner such that the nanobody can be used to deliver cytotoxic agents. Hence, surface thiols can be used as lymphoma biomarkers and targeted by thiol-binding nanobodies. Functionalization of internalizable CB2 is the basis for a range of diagnostic and therapeutic applications of this thiol-binding nanobody.TOC GraphicSynopsisNanobody CB2 specifically binds and internalizes into B cell lymphoma via thiol-based interactions. Functionalized CB2 can be used for complement recruitment or drug delivery to lymphoma cells.
Criticality of neuronal avalanches in human sleep and their relationship with sleep macro- and micro-architecture
Authors: Scarpetta Silvia , Morrisi Niccolò , Mutti Carlotta , Azzi Nicoletta , Trippi Irene , Ciliento Rosario , Apicella Ilenia , Messuti Giovanni , Angiolelli Marianna , Lombardi Fabrizio , Parrino Liborio , Vaudano Anna Elisabetta 
Published: July 2022

AbstractSleep plays a key role in preserving brain function, keeping the brain network in a state that ensures optimal computational capabilities. Empirical evidence indicates that such a state is consistent with criticality, where scale-free neuronal avalanches emerge. However, the relationship between sleep, emergent avalanches, and criticality remains poorly understood. Here we fully characterize the critical behavior of avalanches during sleep, and study their relationship with the sleep macro- and micro-architecture, in particular the cyclic alternating pattern (CAP). We show that avalanche size and duration distributions exhibit robust power laws with exponents approximately equal to −3/2 e −2, respectively. Importantly, we find that sizes scale as a power law of the durations, and that all critical exponents for neuronal avalanches obey robust scaling relations, which are consistent with the mean-field directed percolation universality class. Our analysis demonstrates that avalanche dynamics depends on the position within the NREM-REM cycles, with the avalanche density increasing in the descending phases and decreasing in the ascending phases of sleep cycles. Moreover, we show that, within NREM sleep, avalanche occurrence correlates with CAP activation phases, particularly A1, which are the expression of slow wave sleep propensity and have been proposed to be beneficial for cognitive processes. The results suggest that neuronal avalanches, and thus tuning to criticality, actively contribute to sleep development and play a role in preserving network function. Such findings, alongside characterization of the universality class for avalanches, open new avenues to the investigation of functional role of criticality during sleep with potential clinical application.Significance statementWe fully characterize the critical behavior of neuronal avalanches during sleep, and show that avalanches follow precise scaling laws that are consistent with the mean-field directed percolation universality class. The analysis provides first evidence of a functional relationship between avalanche occurrence, slow-wave sleep dynamics, sleep stage transitions and occurrence of CAP phase A during NREM sleep. Because CAP is considered one of the major guardians of NREM sleep that allows the brain to dynamically react to external perturbation and contributes to the cognitive consolidation processes occurring in sleep, our observations suggest that neuronal avalanches at criticality are associated with flexible response to external inputs and to cognitive processes, a key assumption of the critical brain hypothesis.
Asymmetric learning of dynamic spatial regularities in visual search: facilitation of anticipated target locations, no suppression of predictable distractor locations
Authors: Yu Hao , Allenmark Fredrik , Müller Hermann J. , Shi Zhuanghua 
Published: July 2022

AbstractStatic statistical regularities in the placement of targets and salient distractors within the search display can be learned and used to optimize attentional guidance. Whether statistical learning also extends to dynamic regularities governing the placement of targets and distractors on successive trials has been less investigated. Here, we applied the same dynamic cross-trial regularity (one-step shift of the critical item in clock-/counterclockwise direction) either to the target or a distractor, and additionally varied whether the distractor was defined in a different (color) or the same dimension (shape) as the target. We found robust learning of the predicted target location: processing of the target at this (vs. a random) location was facilitated. But we found no evidence of proactive suppression of the predictable distractor location. Facilitation of the anticipated target location was associated with explicit awareness of the dynamic regularity, whereas participants showed no awareness of the distractor regularity. We propose that this asymmetry arises because, owing to the target’s central role in the task set, its location is explicitly encoded in working memory, enabling the learning of dynamic regularities. In contrast, the distractor is not explicitly encoded; so, statistical learning of distractor locations is limited to static regularities.Public significance statementCan we learn the cross-trial dynamic regularity of a target or a task-irrelevant salient distractor (e.g., one-step shift of the critical item in clock-/counterclockwise direction) to boost search performance? The present study found robust learning of the predicted target location, but no evidence of proactive suppression of the predictable distractor location. Facilitation of the anticipated target location was associated with explicit awareness of the dynamic regularity. This asymmetry highlights the important role of the target-centered task set in the learning of dynamic regularities.
Reference compounds for characterizing cellular injury in high-content cellular morphology assays
Authors: Dahlin Jayme L. , Hua Bruce K. , Zucconi Beth E. , Nelson Shawn D. , Singh Shantanu , Carpenter Anne E. , Shrimp Jonathan H. , Lima-Fernandes Evelyne , Wawer Mathias J. , Chung Lawrence P.W. , Agrawal Ayushi , O’Reilly Mary , Barsyte-Lovejoy Dalia , Szewczyk Magdalena , Li Fengling , Lak Parnian , Cuellar Matthew , Cole Philip A. , Meier Jordan L. , Thomas Tim , Baell Jonathan B. , Brown Peter J. , Walters Michael A. , Clemons Paul A. , Schreiber Stuart L. , Wagner Bridget K. 
Published: July 2022

AbstractRobust, generalizable approaches to identify compounds efficiently with undesirable mechanisms of action in complex cellular assays remain elusive. Such a process would be useful for hit triage during high-throughput screening and, ultimately, predictive toxicology during drug development. We generated cell painting and cellular health profiles for 218 prototypical cytotoxic and nuisance compounds in U-2 OS cells in a concentration-response format. A diversity of compounds causing cellular damage produced bioactive cell painting morphologies, including cytoskeletal poisons, genotoxins, nonspecific electrophiles, and redox-active compounds. Further, we show that lower quality lysine acetyltransferase inhibitors and nonspecific electrophiles can be distinguished from more selective counterparts. We propose that the purposeful inclusion of cytotoxic and nuisance reference compounds such as those profiled in this Resource will help with assay optimization and compound prioritization in complex cellular assays like cell painting.