bluuebunny/crossref_metadata_2025 huggingface dataset:
Separate Spheres: The Gender Division of Labor in the Financial Elite
Authors: Yavorsky Jill E , Keister Lisa A , Qian Yue , Thébaud Sarah
Published: May 2023

In recent decades, the financial elite have seen their economic resources grow significantly, while the income and wealth of other households have stagnated. The financial elite includes couples who are super-rich (top one percent), rich (the 90th–99th percentile), and upper-middle class (the 80th–89th percentile). Gendered work–family arrangements in top economic groups may contribute to inequality—particularly to wealth accumulation among the elite—but relatively little is known about how these couples divide paid and unpaid work or the extent to which their arrangements differ from other couples. In this study, we uncover novel work and family patterns and trends in the most economically powerful families in the United States. We use the Survey of Consumer Finances (1989–2019) to compare the household division of labor across income and wealth groups and over time, with a focus on financial elites. We find stark contrasts between super-rich couples and other couples in the division of labor. Specifically, super-rich couples are much more likely than all other couples, including rich and upper-middle class couples, to have a traditional male breadwinner–female homemaker/caregiver arrangement. Importantly, the striking patterns of traditional arrangements in the top one percent have not changed in 30 years and, as we uncover, appear to be driven by a couple’s wealth rather than income. These findings suggest that work–family arrangements may be an integral component of economic and gender inequality.
Implementation Challenges of T Visa Eligibility for Human Trafficking Survivors: A Role for Social Work
Authors: Carlson William C
Published: May 2023

The passage of the Victims of Trafficking and Violence Protection Act of 2000 (TVPA) and subsequent creation of a residency process for nonresident survivors of human trafficking (the T Visa) are notable milestones in the United States’ effort to address the problem of human trafficking and provide essential supports to trafficking survivors. However, current implementation of the statute’s eligibility criteria for accessing entitlements and protections contributes to a potential for retraumatization, further traumatization, and other continued harms to survivors. The present article explores the structural and conceptual limitations of current T Visa policy and of recent annual policy guidance materials as important contributors to these policy implementation problems. Resulting problems are identified as an ambiguity of definitions and thresholds, a narrow conceptualization of victimhood, and the contradictory relationship between protection and prosecution. This article then utilizes a trauma-informed social policy framework to identify multisystemic action steps for social workers to address these limitations and improve the T Visa process for trafficking survivors. These actions steps provide an essential road map for closing the gap between the policy goals of the TVPA and its current implementation.
Effects of feeding CLOSTAT (Bacillus subtilis PB6) on the clinical health, performance, and carcass characteristics of feedlot steers1
Authors: Ryan Will R , DeSocio Elizabeth S , Youngers Maggie E , Lockard Caleb G , Richards Chris J , Trojan Sara J , Hergenreder Jerilyn E , Wilson Blake K
Published: May 2023

The objectives of this experiment were to evaluate the effects of feeding Bacillus subtilis PB6 on clinical health, performance, and carcass characteristics of feedlot steers. Bos indicus crossbred steer calves (n = 397; 342 kg initial body weight [BW]) were randomly assigned to pens by initial BW; pens (n = 24) were randomly assigned to one of two of the following experimental treatments: 1) no supplemental dietary direct-fed microbial, control (CON; n = 12 pens) or 2) 13 g/steer daily B. subtilis PB6 (CLO; CLOSTAT, Kemin Industries, Des Moines, IA; n = 12 pens). Steers were housed in 12.2 × 30.5 m soil-surfaced pens; pen served as the experimental unit. The percentage of cattle treated once or twice for bovine respiratory disease (BRD) did not differ among treatments (P ≥ 0.27); BRD mortality also did not differ between CON and CLO (P = 0.34). During the receiving period, final BW (P = 0.97), average daily gain (ADG; P = 0.91), dry matter intake (DMI; P = 0.77), and gain:feed (P = 0.79) were not different among treatments. There was a tendency (P = 0.09) for CLO-supplemented steers to be 14% more efficient from days 0 to 14 of the receiving period. Final BW, overall finishing phase ADG, and DMI did not differ by treatment (P ≥ 0.14); ADG was 0.14 kg greater for CLO than CON (P = 0.03) from days 29 to 56 of the finishing period. Gain: feed tended (P = 0.07) to be 7% greater (0.144 vs. 0.141) for CLO than CON throughout the duration of the finishing period, and 6.7% greater (P = 0.08; 0.152 for CLO vs. 0.150 for CON) for the entirety of the experiment. Carcass traits did not differ among treatments (P ≥ 0.31). The results of this experiment suggest that supplementing 13 g/steer daily B. subtilis PB6 may improve feed efficiency in feedlot cattle.
Effects of drought and rehydration on root gene expression in seedlings of Pinus massoniana Lamb.
Authors: Chen Xinhua , Chen Hu , Xu Huilan , Li Mei , Luo Qunfeng , Wang Ting , Yang Zhangqi , Gan Siming
Published: May 2023

The mechanisms underlying plant response to drought involve the expression of numerous functional and regulatory genes. Transcriptome sequencing based on the second- and/or third-generation high-throughput sequencing platforms has proven to be powerful for investigating the transcriptional landscape under drought stress. However, the full-length transcriptomes related to drought responses in the important conifer genus Pinus L. remained to be delineated using the third-generation sequencing technology. With the objectives of identifying the candidate genes responsible for drought and/or rehydration and clarifying the expression profile of key genes involved in drought regulation, we combined the third- and second-generation sequencing techniques to perform transcriptome analysis on seedling roots under drought stress and rewatering in the drought-tolerant conifer Pinus massoniana Lamb. A sum of 294,114 unique full-length transcripts were produced with a mean length of 3217 bp and N50 estimate of 5075 bp, including 279,560 and 124,438 unique full-length transcripts being functionally annotated and Gene Ontology enriched, respectively. A total of 4076, 6295 and 18,093 differentially expressed genes (DEGs) were identified in three pair-wise comparisons of drought-treatment versus control transcriptomes, including 2703, 3576 and 8273 upregulated and 1373, 2719 and 9820 downregulated DEGs, respectively. Moreover, 157, 196 and 691 DEGs were identified as transcription factors in the three transcriptome comparisons and grouped into 26, 34 and 44 transcription factor families, respectively. Gene Ontology enrichment analysis revealed that a remarkable number of DEGs were enriched in soluble sugar-related and cell wall-related processes. A subset of 75, 68 and 97 DEGs were annotated to be associated with starch, sucrose and raffinose metabolism, respectively, while 32 and 70 DEGs were associated with suberin and lignin biosynthesis, respectively. Weighted gene co-expression network analysis revealed modules and hub genes closely related to drought and rehydration. This study provides novel insights into root transcriptomic changes in response to drought dynamics in Masson pine and serves as a fundamental work for further molecular investigation on drought tolerance in conifers.
Beyond Alcohol and Gallstones: Uncommon Causes of Pancreatitis
Authors: McKeown Stephen C. , Keshav Nandan , Thompson William M.
Published: May 2023

Pancreatitis is a major cause of hospital admissions with significant associated morbidity and mortality. Global incidence rates have continued to increase over the last several decades with United States leading the Western world. The most common causes include gallstones for acute pancreatitis and alcohol abuse for both chronic and acute pancreatitis; these are well described in the literature and not infrequently encountered in the day-to-day practice of radiology. Several uncommon pancreatitis causes have unique characteristic patient demographics, clinical presentations, and imaging findings. The unique features relevant to the practice of radiology are discussed for autoimmune pancreatitis, groove pancreatitis, tropical pancreatitis, hereditary pancreatitis, and pancreatic adenocarcinoma presenting as acute pancreatitis with companion cases. The differentiating features of these uncommon causes are emphasized to arrive at a diagnosis. Should imaging remain equivocal, the next steps necessary to arrive at a diagnosis are reviewed. Understanding the various presentations of acute and chronic pancreatitis, both uncommon and common causes are of utmost importance for the practicing radiologist in facilitating management of patient care.
An Analysis of How Herpes Zoster Pain Affects Health-related Quality of Life of Placebo Patients From 3 Randomized Phase III Studies
Authors: Matthews Sean , Curran Desmond , Sabater Cabrera Eliazar , Boutry Céline , Lecrenier Nicolas , Cunningham Anthony L. , Schmader Kenneth
Published: May 2023

Objectives:

Herpes zoster (HZ) is a painful condition caused by the reactivation of the varicella-zoster virus, negatively affecting the lives of patients. In this post hoc analysis, we describe the impact of HZ pain on the health-related quality of life (HRQoL) and activities of daily living (ADL) of immunocompetent individuals 50 years of age and older and in hematopoietic stem cell transplantation (HSCT) recipients age 18 years of age and older.

Materials and Methods:

ZOE-50 (NCT01165177), ZOE-70 (NCT01165229), and ZOE-HSCT (NCT01610414) were phase III, randomized studies conducted in immunocompetent adults 50 years of age and older and 70 years of age and older and in HSCT recipients age 18 years of age and older, respectively. This analysis was performed on patients who experienced an HZ episode in the placebo groups. The impact of varying levels of HZ pain on HRQoL and ADL was analyzed using data from the Zoster Brief Pain Inventory (ZBPI) and the Short Form Health Survey 36 (SF-36) and EQ-5D questionnaires.

Results:

A total of 520 immunocompetent and 172 HSCT individuals with HZ were included. SF-36 and EQ-5D domain scores showed a significant relationship between increased HZ pain and worsening HRQoL. For every increase of 1 in the ZBPI pain score, the estimated mean decrease (worsening) in score in the ZOE-50/70 and ZOE-HSCT, respectively, was 2.0 and 2.4 for SF-36 Role Physical; 2.1 and 1.8 for SF-36 Social Functioning; and 0.041 and 0.045 for EQ-5D utility. Sleep and General activities were the ADL components most affected.

Discussion:

Moderate and severe HZ pain had a substantial negative impact on all aspects of HRQoL and ADL. This impact was independent of age and immunosuppression.
The Association Between Time From Emergency Department Visit to ICU Admission and Mortality in Patients With Sepsis
Authors: Shibata Junichiro , Osawa Itsuki , Fukuchi Kiyoyasu , Goto Tadahiro
Published: May 2023

OBJECTIVES:

The Surviving Sepsis Campaign Guidelines 2021 recommends that adult patients with sepsis requiring intensive care should be admitted to the ICU within 6 hours of their emergency department (ED) visits. However, there is limited evidence on whether 6 hours is the best target time for compliance with the sepsis bundle. We aimed to investigate the association between time from ED visits to ICU admission (i.e., ED length of stay [ED-LOS]) and mortality and identify the optimal ED-LOS for patients with sepsis.

DESIGN:

Retrospective cohort study.

SETTING:

The Medical Information Mart for Intensive Care Emergency Department and Medical Information Mart for Intensive Care IV databases.

PATIENTS:

Adult patients (≥ 18 yr old) who were transferred from the ED to the ICU and subsequently diagnosed with sepsis based on the Sepsis-3 criteria within 24 hours of ICU admission.

INTERVENTIONS:

None.

MEASUREMENTS AND MAIN RESULTS:

Among 1,849 patients with sepsis, we found a disproportionally higher mortality rate in patients immediately admitted to the ICU (e.g., < 2 hr). When using ED-LOS as a continuous variable, ED-LOS was not significantly associated with 28-day mortality (adjusted odds ratio [OR] per hour increase, 1.04; 95% CI, 0.96–1.13; p = 0.3) after an adjustment for potential confounders (e.g., demographics, triage vital signs, and laboratory results) in the multivariable analysis. However, when we categorized all patients into time quartiles (ED-LOS: < 3.3 hr, 3.3–4.5 hr, 4.6–6.1 hr, and > 6.1 hr), patients in the higher time quartiles (e.g., 3.3–4.5 hr) had higher 28-day mortality compared with those in the lowest time quartile (< 3.3 hr) (e.g., adjusted OR for patients in the second time quartile [3.3–4.5 hr] 1.59; 95% CI, 1.03–2.46; p = 0.04).

CONCLUSIONS:

Earlier admission to the ICU (e.g., within 3.3 hr of ED visits) was associated with lower 28-day mortality in patients with sepsis. Our findings suggest patients with sepsis who require intensive care may benefit from a more immediate ICU admission than 6 hours.
Comparator Groups in ICU-Based Studies of Physical Rehabilitation: A Scoping Review of 125 Studies
Authors: O’Grady Heather K. , Reid Julie C. , Farley Christopher , Hanna Quincy E. B. , Unger Janelle , Zorko David J. , Bosch Jackie , Turkstra Lyn S. , Kho Michelle E.
Published: May 2023

OBJECTIVES:

To characterize comparator groups (CGs) in ICU-based studies of physical rehabilitation (PR), including the type, content, and reporting.

DATA SOURCES:

We followed a five-stage scoping review methodology, searching five databases from inception to June 30, 2022. Study selection and data extraction were completed independently, in duplicate.

STUDY SELECTION:

We screened studies by title and abstract, then full-text. We included prospective studies with greater than or equal to two arms enrolling mechanically ventilated adults (≥ 18 yr), with any planned PR intervention initiated in the ICU.

DATA EXTRACTION:

We conducted a quantitative content analysis of authors’ description of CG type and content. We categorized similar CG types (e.g., usual care), classified content into unique activities (e.g., positioning), and summarized these data using counts (proportions). We assessed reporting using Consensus on Exercise Reporting Template (CERT; proportion of reported items/total applicable).

DATA SYNTHESIS:

One hundred twenty-five studies were included, representing 127 CGs. PR was planned in 112 CGs (88.2%; 110 studies), representing four types: usual care (n = 81, 63.8%), alternative treatment than usual care (e.g., different from intervention; n = 18, 14.2%), alternative treatment plus usual care (n = 7, 5.5%), and sham (n = 6, 4.7%). Of 112 CGs with planned PR, 90 CGs (88 studies) reported 60 unique activities, most commonly passive range of motion (n = 47, 52.2%). The remaining 22 CGs (19.6%; 22 studies) reported vague descriptions. PR was not planned in 12 CGs (9.5%; 12 studies), and three CGs (2.4%; three studies) reported no details. Studies reported a median (Q1–Q3) of 46.6% (25.0–73.3%) CERT items. Overall, 20.0% of studies reported no detail to understand planned CG activities.

CONCLUSIONS:

The most common type of CG was usual care. We identified heterogeneity in planned activities and CERT reporting deficiencies. Our results could help guide the selection, design, and reporting of CGs in future ICU-based PR studies.
Real-time ultrasound-guided versus landmark-guided subclavian vein catheterization in the intensive care unit: a prospective randomized study
Authors: Kshirsagar Sujit J. , Naik Sanyogita V. , Pande Anandkumar H. , Bhalerao Pradnya M. , Birnale Chandraprabhu , Thorve Shivprasad
Published: May 2023

Background

The subclavian vein (SCV) is an alternative to the internal jugular vein when it is difficult to locate, such as in patients with hypovolemia or obesity. Ultrasonography (USG) guidance for SVC cannulation has evolved, resulting in fewer complications and higher first-pass success rates. This study aimed to compare the effectiveness and safety of SCV cannulation with USG- and landmark-guided techniques.

Methods

In this prospective randomized interventional controlled study, 80 patients admitted to the intensive care unit between July 2022 and October 2022 were randomly assigned to the landmark method group (LM group) and USG group. In the LM group, SCV cannulation was performed using the traditional landmark technique, whereas in the USG group, it was performed using USG guidance. The primary objective of this study was to evaluate the ease of subclavian central venous cannulation in critically ill patients using the 2 techniques. The secondary objectives were to compare the success rate of cannulation between these 2 techniques, evaluate the number of attempts, assess cannulation failure, and assess mechanical complications.

Results

The first-pass success rates were 70% and 92.5% in the LM and USG groups, respectively (P < 0.001). The average numbers of attempts in the LM and USG groups were 1.275 (±0.520) and 1.075 (±0.266), respectively (P = 0.034). The average procedure durations were 7.45 (±1.10) and 8 (±0.933) minutes in the LM and USG groups (P = 0.018), respectively. The rates of complications in both groups were not statistically significant.

Conclusion

The USG guidance for SCV cannulation has an advantage over landmark-guided methods in a critical care setting. The SCV is a good alternative to internal jugular vein cannulation. The average time to cannulation was longer in the USG group than in the LM group, which can decrease with the frequent use of USG and increasing operator experience.

Clinical trials

This study was registered in the Clinical Trials Registry-India (CTRI Trial No. CTRI/2022/07/043694, dated May 7, 2022).
High dose dexamethasone in high pain responders undergoing total hip arthroplasty
Authors: Nielsen Niklas I. , Kehlet Henrik , Gromov Kirill , Troelsen Anders , Husted Henrik , Varnum Claus , Kjærsgaard-Andersen Per , Rasmussen Lasse E. , Pleckaitiene Lina , Foss Nicolai B.
Published: May 2023

BACKGROUND

Postoperative pain after total hip arthroplasty (THA) may delay postoperative mobilization and discharge. Postoperative pain has been shown to be higher in pain catastrophisers and patients receiving opioids. A single dose of glucocorticoid reduces pain after THA, and an increased dose of glucocorticoids has been found to be effective in patients at high risk of postoperative pain after total knee arthroplasty (TKA), however, the ideal dose in THA remains unknown.

OBJECTIVE

To evaluate the effect of a high dose (1 mg kg−1) vs. intermediate dose (0.3 mg kg−1) of dexamethasone on pain after THA.

DESIGN

A randomized double-blind controlled study.

SETTING

A two-centre study including two large arthroplasty sites in Denmark was conducted from February 2019 to August 2020.

PATIENTS

A total of 160 patients undergoing THA by neuraxial block with multimodal analgesia, having a Pain Catastrophising Scale score >20 and/or preoperative opioid use were included.

INTERVENTION

Patients were randomly assigned to receive dexamethasone 1 mg kg−1 or 0.3 mg kg−1 before THA.

MAIN OUTCOME MEASURES

Primary outcome was percentage of patients experiencing moderate to severe pain (visual analogue scale, VAS > 30 mm on a 0 to 100 mm scale) on ambulating 24 h after surgery. Secondary outcomes included cumulated pain scores, C-reactive protein (CRP), opioid use, postoperative recovery scores, length of stay, complications, and re-admission within 30 and 90 days

RESULTS

No difference was found in percentage of VAS >30 mm 24 h after surgery in the 5-m walk test (VAS > 30/VAS ≤ 30%); 33/42 (44%) vs. 32/43 (43%), relative risk = 1.04 (95% confidence interval 0.72–1.51; P = 0.814) in 1 mg kg−1
vs. 0.3 mg kg−1 respectively. No differences were found in CRP and opioid use between groups. Also, no intergroup differences were found in recovery scores, re-admissions, or complications.

CONCLUSION

1 mg kg−1
vs. 0.3 mg kg−1 dexamethasone improved neither postoperative pain nor recovery in THA in a cohort of predicted high pain responders.

TRIAL REGISTRATION

ClinicalTrials.gov ID-number NCT03763760 and EudraCT-number 2018-2636-25.
Effect of Simultaneous Endothelial Keratoplasty and Cataract Surgery: A Secondary Analysis of the Descemet Endothelial Thickness Comparison Trial
Authors: Chamberlain Winston , Lin Charles C. , Yue Jia , Cavallino Victoria , Benetz Beth Ann , Lass Jonathan H. , Arnold Benjamin , Lietman Thomas M. , Rose-Nussbaumer Jennifer
Published: May 2023

Purpose:

Combining cataract surgery with endothelial keratoplasty (triple EK) is a common practice and may be safer because it commits the patient to only one surgery. This study aimed to determine whether outcomes of pseudophakic endothelial keratoplasty and triple EK have similar outcomes.

Methods:

This was a non-prespecified secondary analysis of a multicenter, double-masked, randomized, controlled clinical trial. Enrollment centers included the Casey Eye Institute at Oregon Health and Sciences University and the Byers Eye Institute at Stanford University. Patients with damaged or diseased endothelium and were considered good candidates for either Descemet membrane endothelial keratoplasty or ultrathin Descemet stripping automated endothelial keratoplasty were randomized to one of the two surgeries 1-2 days prior to surgery. If the patient had a cataract, they underwent simultaneous cataract surgery. The primary outcome was visual acuity at 6 months. Visual acuity at 3, 12, and 24 months, 3, 6, 12, and 24 month endothelial cell density and intraoperative and postoperative complications were also recorded.

Results:

Those who had pseudophakic EK generally were older, more likely to be male, and more likely to have worse baseline vision with higher corneal densitometry values. After controlling for baseline visual acuity and type of keratoplasty, those that underwent Triple-EK had 0.09 better LogMAR lines better visual acuity at 6 (95% CI −0.17 to −0.10; P = 0.02) and 12 months (95% CI −0.21 to −0.07; P = 0.03). Although those receiving Triple- EK had nearly one-half LogMAR line better visual acuity at 24 months, it was no longer statistically significant (95% CI −0.20 to −0.05; P = 0.36). There was no statistically significant difference in ECD between groups at any timepoint. Those undergoing triple EK were more likely to have at least one adverse event (P = 0.02).

Conclusions:

Earlier intervention with Triple-EK may improve visual acuity outcomes after endothelial keratoplasty compared with staged procedures, but may also increase the risks of adverse events including the need for re-bubble.
Alpha Blocker Medical Expulsive Therapy for Ureteral Stones—Usage of Health Care Resources
Authors: Wong Daniel , Vetter Joel , Keller Matthew R. , Palka Joshua , Venkatesh Ramakrishna , Desai Alana
Published: May 2023

Objective:

To study the effects of alpha blocker prescription for ureteral stones on health care resources.

Methods:

In this retrospective study, patients with a new ureteral stone diagnosis were selected from a commercial claims database between 2011 and 2016. We examined data from patients who were and were not prescribed an alpha blocker for ureteral stone diagnosis. Comparative analyses were performed between these groups at 30 and 90 days postdiagnosis. We evaluated the need for surgical intervention, repeat imaging, emergency department (ED) visits, adverse events, and total medical claims cost.

Results:

Of 70,599 patients with ureteral stones, alpha blockers were prescribed to 51.1% for a median duration of ten days. At 30 and 90 days after index diagnosis, alpha blocker treated patients were more likely to undergo surgical intervention (P < .01, 1.06 HR), have additional imaging studies (P < .01, 1.37 HR), and visit the emergency department (P < .01, 1.19 HR). Total medical costs at 30 and 90 days were increased by 11.3% and 10.1%, respectively, for patients treated with an alpha blocker (P < .01).

Conclusions:

Patients who were prescribed an alpha blocker for a diagnosis of ureteral stone had increased surgical interventions, subsequent ED visits, additional imaging studies, and overall total cost to the health care system compared with patients not on alpha blockers. In addition to uncertain and disputed efficacy, the negative impact on health care resources should also be considered in the decision for the use of alpha blockers for ureteral stones.
Prevalence and risk factors for pulmonary embolism in children with sickle cell disease: an institutional retrospective cohort study
Authors: Bala Natasha , Stanek Joseph , Rodriguez Vilmarie , Villella Anthony
Published: May 2023

The study was conducted to examine prevalence of pulmonary embolism in children with sickle cell disease (SCD) and identify potential risk factors associated with pulmonary embolism in a single tertiary paediatric centre.

Children with SCD between 0 and 21 years of age from January 2010 to January 2021 were included. Pulmonary embolism was initially identified using International Classification of Diseases (ICD)-9 or 10 codes and confirmed with manual chart review of identified cases. Logistic regression analysis was performed to assess association between SCD specific and general thrombotic risk factors and pulmonary embolism.

We identified 492 unique patients with SCD with a median age of 11 years (interquartile range: 4–18). A total of eight (1.6%) patients developed a pulmonary embolism. Patients with pulmonary embolism were significantly older (median, interquartile range: 20.5, 14–21 years) than patients without pulmonary embolism (median, interquartile range: 10, 4–17 years). Central nervous system (CNS) vasculopathy and erythrocytapheresis were significantly associated with pulmonary embolism on univariable logistic regression analysis. A previous diagnosis of deep vein thrombosis (DVT) was significantly more common among patients with pulmonary embolism than among those without pulmonary embolism (50 vs. 5.2%; P < 0.0001).

Prevalence of pulmonary embolism in children with SCD was high. Risk factors associated with pulmonary embolism in this study such as CNS vasculopathy or erythrocytapheresis could suggest that the risk for pulmonary embolism in SCD may be related to the severity of disease state. Future studies are needed on pulmonary embolism prevention strategies.
Elderly Pancreatic Adenocarcinoma Cancer Patients Could Benefit From Postoperative Chemotherapy
Authors: Xu Bin , Shi Jinbo , Lu Wenjie , Wu Yulian , Dong Xin
Published: May 2023

Objectives

The study aim to investigate whether elderly patients with resectable pancreatic ductal adenocarcinoma (PDAC) could benefit from postoperative chemotherapy.

Methods

This study selects the data of PDAC patients who were diagnosed between 2004 and 2014 from the Surveillance, Epidemiology, and End Results program. Median overall survival (mOS) is determined by Kaplan-Meier survival curves. Multivariate logistic regression analysis and hazard ratio are employed to assess the association among potential prognostic factors. Propensity score matching evaluation is used to reduce bias.

Results

In total, there are 11,865 PDAC patients selected from the Surveillance, Epidemiology, and End Results database. Elderly PDAC patients have poor prognoses compared with younger (mOS, 15 vs 21 months). The possible reason might be that the elderly patients are less likely to receive postoperative chemotherapy. After propensity score matching, it is found that, for those who receive postoperative chemotherapy, although the mOS of older group is not as good as that of the younger group (mOS, 20 vs 23 months; 18-month survival rate: 53.4% vs 61.3%), the mOS of older group prolonged by postoperative chemotherapy is similar to that of younger group (9 vs 9 months).

Conclusions

Elderly PDAC patients (≥70 years) might benefit from the currently used postoperative chemotherapy regimens.
A Randomized, Double-Blind, Placebo-Controlled Phase 2a Study of Tildrakizumab Efficacy and Safety in Patients With Active Ankylosing Spondylitis
Authors: Peters Eric , Chou Richard C. , Rozzo Stephen J. , Yao Siu-Long , Fructuoso Ferran José García
Published: May 2023

Objective

Tildrakizumab is an anti-interleukin-23p19 monoclonal antibody approved to treat moderate to severe plaque psoriasis. This study evaluated the efficacy and safety of tildrakizumab in patients with ankylosing spondylitis (AS).

Methods

In this randomized, double-blind, parallel-group, multinational trial (clinicaltrials.gov NCT02980705), patients with active AS, according to modified New York criteria and Bath Ankylosing Spondylitis Disease Activity Index Score ≥4, were randomized 1:1 to tildrakizumab 200 mg or placebo every 4 weeks until week 24. Thereafter, all patients received tildrakizumab 200 mg every 4 weeks until week 48. The primary outcome was proportion of patients achieving 20% improvement from baseline by Assessment in SpondyloArthritis International Society criteria (ASAS20) at week 24. This outcome was analyzed in subgroups defined by prior treatment experience, weight, age, and sex using the full analysis set. Safety was assessed through treatment-emergent adverse events.

Results

From December 5, 2017–September 3, 2019, 101 patients (76.2% male, 97% White) enrolled and were randomized to treatment. At week 24, the ASAS20 response rate was 74.0% in patients receiving tildrakizumab 200 mg (n = 50) versus 80.4% in placebo-treated patients (n = 51; treatment difference, −6.31%; 95% confidence interval, −22.34 to 9.71; p = 0.44). No difference in treatment effect by subgroups was observed. Tildrakizumab treatment was generally well tolerated, with no unexpected safety findings. The study was terminated after the week 24 interim analysis due to lack of efficacy.

Conclusions

Tildrakizumab treatment was generally well tolerated but did not improve ASAS20 response rate versus placebo in patients with AS.
Utility of 68Ga-FAPI-04 PET/CT in Adenoid Cystic Carcinoma Compared With 18F-FDG PET/CT
Authors: Civan Caner , Isik Emine Goknur , Has Simsek Duygu , Buyukkaya Fikret , Kuyumcu Serkan
Published: May 2023

68Ga–fibroblast activation protein inhibitor (FAPI) PET/CT is an emerging imaging modality with high sensitivity and high tumor-to-background ratio in various cancers including in the head and neck regions. The authors present 2 cases of adenoid cystic carcinoma who underwent 68Ga-FAPI-04 and 18F-FDG PET/CT. Locoregional recurrence has been detected more precisely in the first case with 68Ga-FAPI-04. In the second case, 68Ga-FAPI-04 outperformed 18F-FDG in the number of lesions and demonstrated intense FAP uptake on widespread metastases, which could provide a treatment option as a theranostic concept. These cases highlight that 68Ga-FAPI-04 PET/CT may be useful for detecting local recurrence and metastases and help select patients for radionuclide treatments targeting cancer-associated fibroblasts.
Inhibition of miR-221-3p promotes axonal regeneration and repair of primary sensory neurons via regulating p27 expression
Authors: Yuan Wenqi , Liu Wei , Zhan Xuehua , Zhou Yueyong , Ma Rong , Liang Simin , Wang Tianyi , Ge Zhaohui
Published: May 2023

This study aimed to explore the key microRNA (miRNA) playing a vital role in axonal regeneration with a hostile microenvironment after spinal cord injury. Based on the theory that sciatic nerve conditioning injury (SNCI) could promote the repair of the injured dorsal column. Differentially expressed miRNAs were screened according to the microarray, revealing that 47 known miRNAs were differentially expressed after injury and perhaps involved in nerve regeneration. Among the 47 miRNAs, the expression of miR-221-3p decreased sharply in the SNCI group compared with the simple dorsal column lesion (SDCL) group. Subsequently, it was confirmed that p27 was the target gene of miR-221-3p from luciferase reporter assay. Further, we found that inhibition of miR-221-3p expression could specifically target p27 to upregulate the expression of growth-associated protein 43 (GAP-43), α-tubulin acetyltransferase (α-TAT1) together with α-tubulin, and advance the regeneration of dorsal root ganglion (DRG) neuronal axons. Chondroitin sulfate proteoglycans (CSPGs) are the main components of glial scar, which can hinder the extension and growth of damaged neuronal axons. After CSPGs were used in this study, the results demonstrated that restrained miR-221-3p expression also via p27 promoted the upregulation of GAP-43, α-TAT1, and α-tubulin and enhanced the axonal growth of DRG neurons. Hence, miR-221-3p could contribute significantly to the regeneration of DRG neurons by specifically regulating p27 in the p27/CDK2/GAP-43 and p27/α-TAT1/α-tubulin pathways even in the inhibitory environment with CSPGs.
Nasopharyngeal carriage and antimicrobial susceptibility profiles of Streptococcus pneumoniae among children with pneumonia and healthy children in Padang, Indonesia
Authors: Yani Finny Fitry , Julianty Riris Juita , Tafroji Wisnu , Linosefa Linosefa , Ihsan Indra , Masnadi Nice Rachmawati , Safari Dodi
Published: May 2023

Streptococcus pneumoniae is one of the pathogenic bacteria causing invasive pneumococcal diseases such as pneumonia, sepsis, and meningitis , which  are commonly reported in children and adults. In this study, we investigated the nasopharyngeal carriage rates, serotype distribution, and antimicrobial susceptibility profiles of S. pneumoniae among children with pneumonia and healthy children under five years old in Padang, West Sumatra, Indonesia.  Nasopharyngeal swabs were collected from 65 hospitalized children with pneumonia in a referral hospital and from 65 healthy children at two Day-care centers from 2018 to 2019. S. pneumoniae was identified by conventional and molecular methods. Antibiotic susceptibility was performed with the disk diffusion method. Out of 130 children, S. pneumoniae strains were carried by 53% and 9.2%  in healthy children (35/65) and children with pneumonia (6/65), respectively. Serotype 19F was the most common serotype among the isolated strains (21%) followed by 6C (10%), 14, 34 (7% each), and 1, 23F, 6A, 6B (5% each). Moreover, 55% of the strains (23/42)  were covered by the 13-valent pneumococcal conjugate vaccine. Most isolates were susceptible to vancomycin (100%), chloramphenicol (93%), clindamycin (76%), erythromycin (71%), and tetracycline (69%). Serotype 19F was commonly found as a multi-drug resistant strain.
Clade 2.3.4.4b H5N1 high pathogenicity avian influenza virus (HPAIV) from the 2021/22 epizootic is highly duck adapted and poorly adapted to chickens
Authors: James Joe , Billington Elizabeth , Warren Caroline J. , De Sliva Dilhani , Di Genova Cecilia , Airey Maisie , Meyer Stephanie M. , Lewis Thomas , Peers-Dent Jacob , Thomas Saumya S. , Lofts Abigail , Furman Natalia , Nunez Alejandro , Slomka Marek J. , Brown Ian H. , Banyard Ashley C.
Published: May 2023

The 2021/2022 epizootic of high pathogenicity avian influenza (HPAIV) remains one of the largest ever in the UK, being caused by a clade 2.3.4.4b H5N1 HPAIV. This epizootic affected more than 145 poultry premises, most likely through independent incursion from infected wild birds, supported by more than 1700 individual detections of H5N1 from wild bird mortalities. Here an H5N1 HPAIV, representative of this epizootic (H5N1-21), was used to investigate its virulence, pathogenesis and transmission in layer chickens and Pekin ducks, two species of epidemiological importance. We inoculated both avian species with decreasing H5N1-21 doses. The virus was highly infectious in ducks, with high infection levels and accompanying shedding of viral RNA, even in ducks inoculated with the lowest dose, reflecting the strong waterfowl adaptation of the clade 2.3.4.4 HPAIVs. Duck-to-duck transmission was very efficient, coupled with high environmental contamination. H5N1-21 was frequently detected in water sources, serving as likely sources of infection for ducks, but inhalable dust and aerosols represented low transmission risks. In contrast, chickens inoculated with the highest dose exhibited lower rates of infection compared to ducks. There was no evidence for experimental H5N1-21 transmission to any naive chickens, in two stocking density scenarios, coupled with minimal and infrequent contamination being detected in the chicken environment. Systemic viral dissemination to multiple organs reflected the pathogenesis and high mortalities in both species. In summary, the H5N1-21 virus is highly infectious and transmissible in anseriformes, yet comparatively poorly adapted to galliformes, supporting strong host preferences for wild waterfowl. Key environmental matrices were also identified as being important in the epidemiological spread of this virus during the continuing epizootic.
Discovery and biosynthetic assessment of 'Streptomyces ortus' sp. nov. isolated from a deep-sea sponge
Authors: Williams Sam E. , Back Catherine R. , Best Eleanor , Mantell Judith , Stach James E. M. , Williams Tom A. , Race Paul R. , Curnow Paul
Published: May 2023

The deep sea is known to host novel bacteria with the potential to produce a diverse array of undiscovered natural products. Thus, understanding these bacteria is of broad interest in ecology and could also underpin applied drug discovery, specifically in the area of antimicrobials. Here, we isolate a new strain of

Streptomyces

from the tissue of the deep-sea sponge Polymastia corticata collected at a depth of 1869 m from the Gramberg Seamount in the Atlantic Ocean. This strain, which was given the initial designation A15ISP2-DRY2T, has a genome size of 9.29 Mb with a G+C content of 70.83 mol%. Phylogenomics determined that A15ISP2-DRY2T represents a novel species within the genus

Streptomyces

as part of the

Streptomyces aurantiacus

clade. The biosynthetic potential of A15ISP2-DRY2T was assessed relative to other members of the

S

.

aurantiacus

clade via comparative gene cluster family (GCF) analysis. This revealed a clear congruent relationship between phylogeny and GCF content. A15ISP2-DRY2T contains six unique GCFs absent elsewhere in the clade. Culture-based assays were used to demonstrate the antibacterial activity of A15ISP2-DRY2T against two drug-resistant human pathogens. Thus, we determine A15ISP2-DRY2T to be a novel bacterial species with considerable biosynthetic potential and propose the systematic name 'Streptomyces ortus' sp. nov.
Retrospective Analysis of Equity-Based Optimization for COVID-19 Vaccine Allocation
Authors: Stafford Erin , Dimitrov Dobromir , Ceballos Rachel , Campelia Georgina , Matrajt Laura
Published: May 2023

Marginalized racial and ethnic groups in the United States were disproportionally affected by the COVID-19 pandemic. To study these disparities, we construct an age-and-race-stratified mathematical model of SARS-CoV-2 transmission fitted to age-and-race-stratified data from 2020 in Oregon and analyze counter-factual vaccination strategies in early 2021. We consider two racial groups: non-Hispanic White persons and persons belonging to BIPOC groups (including non-Hispanic Black persons, non-Hispanic Asian persons, non-Hispanic American Indian or Alaska Native persons, and Hispanic or Latino persons). We allocate a limited amount of vaccine to minimize overall disease burden (deaths or years of life lost), inequity in disease outcomes between racial groups (measured with five different metrics), or both. We find that, when allocating small amounts of vaccine (10% coverage), there is a trade-off between minimizing disease burden and minimizing inequity. Older age groups, who are at a greater risk of severe disease and death, are prioritized when minimizing measures of disease burden, and younger BIPOC groups, who face the most inequities, are prioritized when minimizing measures of inequity. The allocation strategies that minimize combinations of measures can produce middle-ground solutions that similarly improve both disease burden and inequity, but the trade-off can only be mitigated by increasing the vaccine supply. With enough resources to vaccinate 20% of the population the trade-off lessens, and with 30% coverage, we can optimize both equity and mortality. Our goal is to provide a race-conscious framework to quantify and minimize inequity that can be used for future pandemics and other public health interventions.
Side-Chain Dynamics of the α1B-Adrenergic Receptor determined by NMR via Methyl Relaxation
Authors: Baumann Christian , Chiang Wan-Chin , Valsecchi Renato , Jurt Simon , Deluigi Mattia , Schuster Matthias , Plückthun Andreas , Zerbe Oliver
Published: May 2023

G protein-coupled receptors (GPCRs) are medically important membrane proteins that sample inactive, intermediate, and active conformational states characterized by relatively slow interconversions (∼μs– ms). On a faster timescale (∼ps–ns), the conformational landscape of GPCRs is governed by the rapid dynamics of amino acid side chains. Such dynamics are essential for protein functions such as ligand recognition and allostery. Unfortunately, technical challenges have almost entirely precluded the study of side-chain dynamics for GPCRs. Here, we investigate the rapid side-chain dynamics of a thermostabilized α1B-adrenergic receptor (α1B-AR) as probed by methyl relaxation. We determined order parameters for Ile, Leu, and Val methyl groups in the presence of inverse agonists that bind orthosterically (prazosin, tamsulosin) or allosterically (conopeptide ρ-TIA). Despite the differences in the ligands, the receptor’s overall side-chain dynamics are very similar, including those of the apo form. However, ρ-TIA increases the flexibility of Ile1764x56and possibly of Ile2145x49, adjacent to Pro2155x50of the highly conserved P5x50I3x40F6x44motif crucial for receptor activation, suggesting differences in the mechanisms for orthosteric and allosteric receptor inactivation. Overall, increased Ile side-chain rigidity was found for residues closer to the center of the membrane bilayer, correlating with denser packing and lower protein surface exposure. In contrast to two microbial membrane proteins, in α1B-AR Leu exhibited higher flexibility than Ile side chains on average, correlating with the presence of Leu in less densely packed areas and with higher protein-surface exposure than Ile. Our findings demonstrate the feasibility of studying receptor-wide side-chain dynamics in GPCRs to gain functional insights.
Immune-induced remodelling of mRNA structurome regulates uORF-mediated translation
Authors: Xiang Yezi , Chen Tianyuan , Irving Patrick S. , Weeks Kevin M. , Dong Xinnian
Published: May 2023

To survive stress, eukaryotes selectively translate stress-related transcripts while inhibiting growth-associated protein production. How this translational reprogramming occurs under biotic stress has not been systematically studied. To identify common features shared by transcripts with stress-upregulated translation efficiency (TE-up), we first performed high-resolution ribosome-sequencing inArabidopsisduring pattern-triggered immunity and found that TE-up transcripts are enriched with upstream open reading frames (uORFs). Under non-stress conditions, start codons of these uORFs (uAUGs) have higher-than-background ribosomal association. Upon immune induction, there is an overall downshift in ribosome occupancy at uAUGs, accompanied by enhanced translation of main ORFs (mORFs). Usingin plantanucleotide-resolution mRNA structurome probing, we discovered that this stress-induced switch in translation is mediated by highly structured regions detected downstream of uAUGs in TE-up transcripts. Without stress, these structures are responsible for uORF-mediated inhibition of mORF translation by slowing progression of the translation preinitiation complex to initiate translation from uAUGs, instead of mAUGs. In response to immune induction, uORF-inhibition is alleviated by three Ded1p/DDX3X-homologous RNA helicases which unwind the RNA structures, allowing ribosomes to bypass the inhibitory uORFs and upregulate defence protein production. Conservation of the RNA helicases suggests that mRNA structurome remodelling is a general mechanism for stress-induced translation across kingdoms.
Universal method for the gentle isolation of intact microvessels from frozen tissue: a multiomic investigation into the neurovasculature
Authors: Wakid Marina , Almeida Daniel , Aouabed Zahia , Rahimian Reza , Davoli Maria Antonietta , Yerko Volodymyr , Leonova-Erko Elena , Richard Vincent , Zahedi René , Borchers Christoph , Turecki Gustavo , Mechawar Naguib
Published: May 2023

The neurovascular unit (NVU), comprised of endothelial cells, pericytes, smooth muscle cells, astrocytic endfeet and microglia together with neurons, is paramount for the proper function of the central nervous system. The NVU gatekeeps blood-brain barrier (BBB) properties which, as a system, experiences impairment in several neurological and psychiatric diseases, and contributes to pathogenesis. To better understand function and dysfunction at the NVU, isolation and characterization of the NVU is needed. Here, we describe a singular, standardized protocol to enrich and isolate microvessels from archived snap-frozen human and frozen mouse cerebral cortex using mechanical homogenization and centrifugation-separation that preserves the structural integrity and multicellular composition of microvessel fragments. For the first time, microvessels are isolated from postmortem vmPFC tissue and are comprehensively investigated using both RNA sequencing and Liquid Chromatography with tandem mass spectrometry (LC-MS-MS). Both the transcriptome and proteome are elucidated and compared, demonstrating that the isolated brain microvessel is a robust model for the NVU and can be used to generate highly informative datasets in both physiological and disease contexts.