bluuebunny/crossref_metadata_2025_split huggingface dataset:
HER2 Expression Associated with Clinical Characteristics and Prognosis of Urothelial Carcinoma in a Chinese Population
Authors: Zhou Li , Shao Zhiting , Liu Yiqiang , Yan Xieqiao , Li Juan , Wu Xiaowen , Tang Bixia , Li Siming , Cui Chuanliang , Chi Zhihong , Si Lu , Kong Yan , Mao Lili , Lian Bin , Wang Xuan , Bai Xue , Dai Jie , Guo Jun , Sheng Xinan 
Published: March 2023

Abstract

Background
The frequency of HER2 overexpression in bladder cancer is reported as 9%-61%. HER2 alteration correlates with aggressive disease in bladder cancer. Traditional anti-HER2 targeted therapy has failed to show clinical benefits in patients with advanced urothelial carcinoma .

Methods
The information on pathologically proven patients with urothelial carcinoma with detected HER2 status was collected from the database of Peking University Cancer Hospital. The HER2 expression, as well as its association with clinical characteristics and prognosis, was analyzed.

Results
A total of 284 consecutive patients with urothelial carcinoma were enrolled. HER2 was positive (IHC 2+/3+) in 44% of urothelial carcinoma. HER2 positivity was found more frequent in UCB than in UTUC (51% vs. 38%). Stage, radical surgery, and histological variant were associated with survival (P &lt; .05). For metastatic patients, multivariate analysis shows that 3 indicators, including liver metastasis, the number of involved organs, and anemia, are independent risk factors of prognosis. Receiving immunotherapy or disitamab vedotin (DV) treatment is an independent protecting factor. The survival of patients with low HER2 expression was also significantly improved by the treatment of DV (P &lt; .001). HER2 expression (IHC 1+, 2+, 3+) was associated with a better prognosis in this population.

Conclusion
DV has improved the survival of patients with urothelial carcinoma in the real world. With the new-generation anti-HER2 ADC treatment, HER2 expression is no longer a poor prognostic factor.
Efficacy and Safety of Adjuvant Radiotherapy in Re-excised Soft-tissue Sarcoma After Unplanned Resection
Authors: Allignet Benoît , Pou Paul , Izarn Floriane , Ray-Coquard Isabelle , Blay Jean-Yves , Dufresne Armelle , Brahmi Mehdi , Bouhamama Amine , Meeus Pierre , Vaz Gualter , Gouin Francois , Meurgey Alexandra , Karanian Marie , Moncharmont Coralie , Waissi Waisse , Sunyach Marie-Pierre 
Published: March 2023

Abstract

Introduction
The objective of this study was to evaluate the efficacy and safety of adjuvant radiotherapy (aRT) in patients with soft-tissue sarcoma (STS) re-excised after unplanned tumor resection (UPR).

Materials and Methods
From 2000 to 2015, we retrospectively evaluated patients with STS of limb or trunk who underwent post-UPR re-excision in our expert center and received or not aRT.

Results
Median follow-up was 121 months (IQR 94-165). Among the 145 patients, 37 were not treated with aRT (no-RT) and 108 received aRT with a median radiation dose of 50 Gy (IQR 50-60). At 10 years, patients in the aRT and no-RT groups showed a cumulative incidence of local failure (10y-LF) of 14.7% and 37.7%, and a local recurrence-free survival (10y-LRFS) of 61.3% and 45.8%, respectively. Multivariate analysis identified aRT and age ≥70 years as independent predictors of both LF and LRFS, while grade 3 and deep-seated tumor were independent predictors of LRFS. In overall population, 10-year distant metastasis-free survival (10y-DMFS) and overall survival (10y-OS) were 63.7% and 69.4%. In multivariate analyses, age ≥70 years, grade 3, and deep-seated lesion were associated with shorter DMFS and OS. Acute severe adverse events were not significantly increased in aRT group (14.8% vs. 18.1%, P = .85) but dramatically increased if radiation dose exceeded 50 Gy (risk ratio 2.96 compared to ≤50 Gy, P = .04).

Conclusion
In STS patients re-excised after UPR, 50 Gy aRT was safe and associated with reduced LF and longer LRFS. It seems to be beneficial even in absence of residual disease or in absence of initial adverse prognostic factors.
Protein S-acylation controls the subcellular localization and biological activity of PHYTOCHROME KINASE SUBSTRATE
Authors: Lopez Vazquez Ana , Allenbach Petrolati Laure , Legris Martina , Dessimoz Christophe , Lampugnani Edwin R , Glover Natasha , Fankhauser Christian 
Published: March 2023

Abstract
PHYTOCHROME KINASE SUBSTRATE (PKS) proteins are involved in light-modulated changes in growth orientation. They act downstream of phytochromes to control hypocotyl gravitropism in the light and act early in phototropin signaling. Despite their importance for plant development, little is known about their molecular mode of action, except that they belong to a protein complex comprising phototropins at the plasma membrane (PM). Identifying evolutionary conservation is one approach to revealing biologically important protein motifs. Here, we show that PKS sequences are restricted to seed plants and that these proteins share 6 motifs (A to F from the N to the C terminus). Motifs A and D are also present in BIG GRAIN, while the remaining 4 are specific to PKSs. We provide evidence that motif C is S-acylated on highly conserved cysteines, which mediates the association of PKS proteins with the PM. Motif C is also required for PKS4-mediated phototropism and light-regulated hypocotyl gravitropism. Finally, our data suggest that the mode of PKS4 association with the PM is important for its biological activity. Our work, therefore, identifies conserved cysteines contributing to PM association of PKS proteins and strongly suggests that this is their site of action to modulate environmentally regulated organ positioning.
Do Short Sellers Affect Corporate Innovation? Evidence from a Policy Experiment
Authors: He Jie (Jack) , Ren Xiao (Shaun) , Tian Xuan 
Published: March 2023

Abstract
We examine the effect of short sellers on corporate innovation. To establish causality, we use a policy experiment that exogenously removes the short-selling constraint for a randomly selected subsample of Russell 3000 firms. We find that innovation quality, value, and efficiency of treatment firms improve significantly more than those of control firms surrounding the policy shock. The exposure to patenting-related litigation initiated by short sellers is a plausible underlying mechanism through which short sellers discipline firm managers and enhance innovation. Our paper provides new insights into an unintended real effect of short sellers, specifically their improvement of technological innovation. (JEL G14, G18, G34, K22, O31, O32)
Benzodiazepine, Z-drug, and sleep medication prescriptions in male and female people with opioid use disorder on buprenorphine and comorbid insomnia: an analysis of multistate insurance claims
Authors: Martin Caitlin E , Patel Hetal , Dzierzewski Joseph M , Moeller F Gerard , Bierut Laura J , Grucza Richard A , Xu Kevin Y 
Published: March 2023

Abstract

Study Objectives
In adult populations, women are more likely than men to be prescribed benzodiazepines. However, such disparities have not been investigated in people with opioid use disorder (OUD) and insomnia receiving buprenorphine, a population with particularly high sedative/hypnotic receipt. This retrospective cohort study used administrative claims data from Merative MarketScan Commercial and MultiState Medicaid Databases (2006–2016) to investigate sex differences in the receipt of insomnia medication prescriptions among patients in OUD treatment with buprenorphine.

Methods
We included people aged 12–64 years with diagnoses of insomnia and OUD-initiating buprenorphine during the study timeframe. The predictor variable was sex (female versus male). The primary outcome was receipt of insomnia medication prescription within 60 days of buprenorphine start, encompassing benzodiazepines, Z-drugs, or non-sedative/hypnotic insomnia medications (e.g. hydroxyzine, trazodone, and mirtazapine). Associations between sex and benzodiazepine, Z-drug, and other insomnia medication prescription receipt were estimated using Poisson regression models.

Results
Our sample included 9510 individuals (female n = 4637; male n = 4873) initiating buprenorphine for OUD who also had insomnia, of whom 6569 (69.1%) received benzodiazepines, 3891 (40.9%) Z-drugs, and 8441 (88.8%) non-sedative/hypnotic medications. Poisson regression models, adjusting for sex differences in psychiatric comorbidities, found female sex to be associated with a slightly increased likelihood of prescription receipt: benzodiazepines (risk ratio [RR], RR = 1.17 [1.11–1.23]), Z-drugs (RR = 1.26 [1.18–1.34]), and non-sedative/hypnotic insomnia medication (RR = 1.07, [1.02–1.12]).

Conclusions
Sleep medications are commonly being prescribed to individuals with insomnia in OUD treatment with buprenorphine, with sex-based disparities indicating a higher prescribing impact among female than male OUD treatment patients.
“We’re Better than Most”: Diversity Discourse in the San Francisco Bay Area Tech Industry
Authors: Luhr Sigrid 
Published: March 2023

Abstract
Despite recent efforts to diversify their workplaces, tech companies remain predominantly White, Asian, and male—drawing on in-depth interviews with 50 tech workers in the San Francisco Bay Area, this article examines how these workers think about the term “diversity” with respect to their own companies. While previous research on diversity within organizations largely centers on Human Resource professionals or policy makers, this article unpacks how workers themselves define and discuss diversity. Although most respondents acknowledged a “diversity problem” in the tech industry, they saw their own companies as “better than most.” They made this claim by 1) drawing relative comparisons with other tech companies; 2) citing evidence of efforts their companies were making to increase diversity; and 3) using expansive definitions of the term “diversity.” Yet perceiving their companies as “better than most” may breed a kind of complacency where workers consider their companies “above average” on diversity when they look similar to other companies. These interviews provide evidence that the diversity initiatives at tech companies – while not necessarily effective in reducing racial or gender inequality – are effective in convincing some workers that their companies are diverse. This article provides insight into why efforts to increase diversity within organizations may stall.
Mesenchymal Stromal Cells Suppress T-Cell-Mediated Delayed-Type Hypersensitivity via ALCAM-CD6 Interaction
Authors: Cho WonKyung J , Mittal Sharad K , Chauhan Sunil K 
Published: March 2023

AbstractMounting evidence suggests mesenchymal stromal cells (MSCs) suppress CD4+ T-cell activation, but whether MSCs directly regulate activation and expansion of allogeneic T cells has not been fully deciphered. Here, we identified that both human and murine MSCs constitutively express ALCAM, a cognate ligand for CD6 receptors on T cells, and investigated its immunomodulatory function using in vivo and in vitro experiments. Our controlled coculture assays demonstrated that ALCAM-CD6 pathway is critical for MSCs to exert its suppressive function on early CD4+CD25− T-cell activation. Moreover, neutralizing ALCAM or CD6 results in the abrogation of MSC-mediated suppression of T-cell expansion. Using a murine model of delayed-type hypersensitivity response to alloantigen, we show that ALCAM-silenced MSCs lose the capacity to suppress the generation of alloreactive IFNγ-secreting T cells. Consequently, MSCs, following ALCAM knockdown, failed to prevent allosensitization and alloreactive T-cell-mediated tissue damage.
SATB1 Chromatin Loops Regulate Megakaryocyte/Erythroid Progenitor Expansion by Facilitating HSP70 and GATA1 Induction
Authors: Wilkes Mark C , Chae Hee-Don , Scanlon Vanessa , Cepika Alma-Martina , Wentworth Ethan P , Saxena Mallika , Eskin Ascia , Chen Zugen , Glader Bert , Grazia Roncarolo Maria , Nelson Stanley F , Sakamoto Kathleen M 
Published: March 2023

Abstract
Diamond Blackfan anemia (DBA) is an inherited bone marrow failure syndrome associated with severe anemia, congenital malformations, and an increased risk of developing cancer. The chromatin-binding special AT-rich sequence-binding protein-1 (SATB1) is downregulated in megakaryocyte/erythroid progenitors (MEPs) in patients and cell models of DBA, leading to a reduction in MEP expansion. Here we demonstrate that SATB1 expression is required for the upregulation of the critical erythroid factors heat shock protein 70 (HSP70) and GATA1 which accompanies MEP differentiation. SATB1 binding to specific sites surrounding the HSP70 genes promotes chromatin loops that are required for the induction of HSP70, which, in turn, promotes GATA1 induction. This demonstrates that SATB1, although gradually downregulated during myelopoiesis, maintains a biological function in early myeloid progenitors.
Performance Assessment of the American College of Surgeons Risk Calculator in Metastatic Spinal Tumor Surgery
Authors: Ryvlin Jessica , Hamad Mousa K. , Wang Benjamin , Xavier Jorden , De la Garza Ramos Rafael , Murthy Saikiran G. , Gelfand Yaroslav , Yassari Reza 
Published: March 2023

Study Design.
This was a retrospective cohort study.

Objective.
The objective of this study was to assess the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) surgical risk calculator performance in patients undergoing surgery for metastatic spine disease.

Summary of Background Data.
Patients with spinal metastases may require surgical intervention for cord compression or mechanical instability. The ACS-NSQIP calculator was developed to assist surgeons with estimating 30-day postoperative complications based on patient-specific risk factors and has been validated within several surgical patient populations.

Materials and Methods.
We included 148 consecutive patients at our institution who underwent surgery for metastatic spine disease between 2012 and 2022. Our outcomes were 30-day mortality, 30-day major complications, and length of hospital stay (LOS). Predicted risk, determined by the calculator, was compared with observed outcomes using receiver operating characteristic curves with area under the curve (AUC) and Wilcoxon signed-rank tests. Analyses were repeated using individual corpectomy and laminectomy Current Procedural Terminology (CPT) codes to determine procedure-specific accuracy.

Results.
Based on the ACS-NSQIP calculator, there was good discrimination between observed and predicted 30-day mortality incidence overall (AUC=0.749), as well as in corpectomy cases (AUC=0.745) and laminectomy cases (AUC=0.788). Poor 30-day major complication discrimination was seen in all procedural cohorts, including overall (AUC=0.570), corpectomy (AUC=0.555), and laminectomy (AUC=0.623). The overall median observed LOS was similar to predicted LOS (9 vs. 8.5 d, P=0.125). Observed and predicted LOS were also similar in corpectomy cases (8 vs. 9 d; P=0.937) but not in laminectomy cases (10 vs. 7 d, P=0.012).

Conclusions.
The ACS-NSQIP risk calculator was found to accurately predict 30-day postoperative mortality but not 30-day major complications. The calculator was also accurate in predicting LOS following corpectomy but not laminectomy. While this tool may be utilized to predict risk short-term mortality in this population, its clinical value for other outcomes is limited.
Patient-Centered Outcomes Following Prone Lateral Single-Position Approach to Same-Day Circumferential Spine Surgery
Authors: Passias Peter G. , Williamson Tyler K. , Krol Oscar , Joujon-Roche Rachel , Imbo Bailey , Tretiakov Peter , Ahmad Salman , Bennett-Caso Claudia , Lebovic Jordan , Owusu-Sarpong Stephane , Park Paul , Chou Dean , Vira Shaleen , Diebo Bassel G. , Schoenfeld Andrew J. 
Published: March 2023

Study Design.
Retrospective study

Objective.
Evaluate surgical characteristics and postoperative 2-year results of the PL approach to spinal fusion

Summary of Background Data.
Prone-lateral(PL) single positioning has recently gained popularity in spine surgery due to lower blood loss and operative time, but has yet to be examined for other notable outcomes, including realignment and patient-reported measures.

Methods.
We included circumferential spine fusion patients with minimum one-year follow-up. Patients stratified into groups based on undergoing PL approach versus same-day staged(Staged). Means comparison tests identified differences in baseline parameters. Multivariable logistic regression, controlling for age, levels fused, and Charlson Comorbidity Index(CCI) was used to determine the influence of approach on complication rates, radiographic and patient-reported outcomes up to two years.

Results.
122 patients were included. 72(59%) same-day staged and 50(41%) PL. PL patients were older with lower BMI(both P<0.05). Patients undergoing PL procedures had lower EBL and operative time(both P<0.001), along with fewer osteotomies(63% vs. 91%,P<0.001). This translated to shorter length of stay(3.8 d vs. 4.9,P=0.041). PL procedures demonstrated better correction in both PT(4.0 vs. −0.2,P=0.033 and PI-LL(−3.7 vs. 3.1,P=0.012). PL procedures were more likely to improve in GAP relative pelvic version(OR: 2.3,[1.5-8.8];P=0.003]. PL patients suffered less complications during the perioperative period and greater improvement in NRS-Back(−6.0 vs. −3.3,P=0.031), with less reoperations(0.0% vs. 4.8%,P=0.040) by two years.

Conclusions.
Patients undergoing prone lateral single position procedures received less invasive procedures with better correction of pelvic compensation, as well as earlier discharge. The prone lateral cohort also demonstrated greater clinical improvement and lower rate of reoperations by two years following spinal corrective surgery.

Level of Evidence.
III
Limiting Dynamic Driving Pressure in Patients Requiring Mechanical Ventilation*
Authors: Urner Martin , Jüni Peter , Rojas-Saunero L. Paloma , Hansen Bettina , Brochard Laurent J. , Ferguson Niall D. , Fan Eddy 
Published: March 2023

Objectives:
Previous studies reported an association between higher driving pressure (∆P) and increased mortality for different groups of mechanically ventilated patients. However, it remained unclear if sustained intervention on ∆P, in addition to traditional lung-protective ventilation, improves outcomes. We investigated if ventilation strategies limiting daily static or dynamic ∆P reduce mortality compared with usual care in adult patients requiring greater than or equal to 24 hours of mechanical ventilation.

Design:
For this comparative effectiveness study, we emulated pragmatic clinical trials using data from the Toronto Intensive Care Observational Registry recorded between April 2014 and August 2021. The per-protocol effect of the interventions was estimated using the parametric g-formula, a method that controls for baseline and time-varying confounding, as well as for competing events in the analysis of longitudinal exposures.

Setting:
Nine ICUs from seven University of Toronto-affiliated hospitals.

Patients:
Adult patients (≥18 yr) requiring greater than or equal to 24 hours of mechanical ventilation.

Interventions:
Receipt of a ventilation strategy that limited either daily static or dynamic ∆P less than or equal to 15 cm H2O compared with usual care.

Measurements and Main Results:
Among the 12,865 eligible patients, 4,468 of (35%) were ventilated with dynamic ∆P greater than 15 cm H2O at baseline. Mortality under usual care was 20.1% (95% CI, 19.4–20.9%). Limiting daily dynamic ∆P less than or equal to 15 cm H2O in addition to traditional lung-protective ventilation reduced adherence-adjusted mortality to 18.1% (95% CI, 17.5–18.9%) (risk ratio, 0.90; 95% CI, 0.89–0.92). In further analyses, this effect was most pronounced for early and sustained interventions. Static ∆P at baseline were recorded in only 2,473 patients but similar effects were observed. Conversely, strict interventions on tidal volumes or peak inspiratory pressures, irrespective of ∆P, did not reduce mortality compared with usual care.

Conclusions:
Limiting either static or dynamic ∆P can further reduce the mortality of patients requiring mechanical ventilation.
Implementation of Video Laryngoscope-Assisted Coaching Reduces Adverse Tracheal Intubation-Associated Events in the PICU*
Authors: Giuliano John , Krishna Ashwin , Napolitano Natalie , Panisello Josep , Shenoi Asha , Sanders Ronald C. , Rehder Kyle , Al-Subu Awni , Brown Calvin , Edwards Lauren , Wright Lisa , Pinto Matthew , Harwayne-Gidansky Ilana , Parsons Simon , Romer Amy , Laverriere Elizabeth , Shults Justine , Yamada Nicole K. , Walsh Catharine M. , Nadkarni Vinay , Nishisaki Akira ,   for the National Emergency Airway Registry for Children (NEAR4KIDS) and Pediatric Acute Lung Injury and Sepsis Investigators (PALISI) Network
Published: March 2023

Objectives:
To evaluate implementation of a video laryngoscope (VL) as a coaching device to reduce adverse tracheal intubation associated events (TIAEs).

Design:
Prospective multicenter interventional quality improvement study.

Setting:
Ten PICUs in North America.

Patients:
Patients undergoing tracheal intubation in the PICU.

Interventions:
VLs were implemented as coaching devices with standardized coaching language between 2016 and 2020. Laryngoscopists were encouraged to perform direct laryngoscopy with video images only available in real-time for experienced supervising clinician-coaches.

Measurements and Main Results:
The primary outcome was TIAEs. Secondary outcomes included severe TIAEs, severe hypoxemia (oxygen saturation < 80%), and first attempt success. Of 5,060 tracheal intubations, a VL was used in 3,580 (71%). VL use increased from baseline (29.7%) to implementation phase (89.4%; p < 0.001). VL use was associated with lower TIAEs (VL 336/3,580 [9.4%] vs standard laryngoscope [SL] 215/1,480 [14.5%]; absolute difference, 5.1%; 95% CI, 3.1–7.2%; p < 0.001). VL use was associated with lower severe TIAE rate (VL 3.9% vs SL 5.3%; p = 0.024), but not associated with a reduction in severe hypoxemia (VL 15.7% vs SL 16.4%; p = 0.58). VL use was associated with higher first attempt success (VL 71.8% vs SL 66.6%; p < 0.001). In the primary analysis after adjusting for site clustering, VL use was associated with lower adverse TIAEs (odds ratio [OR], 0.61; 95% CI, 0.46–0.81; p = 0.001). In secondary analyses, VL use was not significantly associated with severe TIAEs (OR, 0.72; 95% CI, 0.44–1.19; p = 0.20), severe hypoxemia (OR, 0.95; 95% CI, 0.73–1.25; p = 0.734), or first attempt success (OR, 1.28; 95% CI, 0.98–1.67; p = 0.073). After further controlling for patient and provider characteristics, VL use was independently associated with a lower TIAE rate (adjusted OR, 0.65; 95% CI, 0.49–0.86; p = 0.003).

Conclusions:
Implementation of VL-assisted coaching achieved a high level of adherence across the PICUs. VL use was associated with reduced adverse TIAEs.