bluuebunny/crossref_metadata_2025 huggingface dataset:
IMPROVE bleeding score predicts major bleeding in advanced gastrointestinal cancer patients with venous thromboembolism
Authors: Kusaba Hitoshi , Moriyama Shohei , Hieda Michinari , Ito Mamoru , Ohmura Hirofumi , Isobe Taichi , Tsuchihashi Kenji , Fukata Mitsuhiro , Ariyama Hiroshi , Baba Eishi
Published: June 2022

Background

The incidence of venous thromboembolism has been reported as 20% in cancer patients. Anticoagulation therapy is the standard treatment for venous thromboembolism. On the other hand, bleeding should be carefully managed, because advanced cancer, particularly gastrointestinal cancer, carries a high risk of bleeding. However, the optimal management for cancer-associated thromboembolism remains to be clarified.

Methods

We retrospectively examined patients with advanced gastrointestinal cancer, including gastric cancer and colorectal cancer, who were treated with chemotherapy between 2014 and 2018 for the incidence and characteristics of venous thromboembolism and bleeding.

Results

In total, 194 patients (120 men, 74 women) were enrolled in this study. The underlying pathology was gastric cancer in 74 cases and colorectal cancer in 120 cases. Of the 194 patients, 40 patients (20.6%) were diagnosed with venous thromboembolism and 10 patients (5.2%) were diagnosed with concomitant pulmonary thromboembolism. Conversely, bleeding was observed in 29 patients (15%). The location of bleeding was the primary tumor in 17 cases, metastatic tumor in 9 and hemorrhagic gastric ulcer in 3. Within the venous thromboembolism group (n = 40), bleeding was observed in 10 patients (25%). Multivariate analysis showed that International Medical Prevention Registry on Venous Thromboembolism (IMPROVE) bleeding score ≥7 correlated significantly with major bleeding (P = 0.01). In patients with a low risk of bleeding, major bleeding was observed in only three patients.

Conclusions

IMPROVE bleeding score may predict the risk for bleeding in gastrointestinal cancer patients with venous thromboembolism. Selecting patients with a low risk of bleeding using with IMPROVE bleeding score is expected to contribute to the safer management of anticoagulation therapy for cancer-associated thromboembolism.
Pulsar wind nebulae of runaway massive stars
Authors: Meyer D M-A , Meliani Z
Published: June 2022

A significant fraction of massive stars move at speed through the interstellar medium of galaxies. After their death as core-collapse supernovae, a possible final evolutionary state is that of a fast-rotating magnetized neutron star, shaping its circumstellar medium into a pulsar wind nebula. Understanding the properties of pulsar wind nebulae requires knowledge of the evolutionary history of their massive progenitors. Using two-dimensional magnetohydrodynamical simulations, we demonstrate that, in the context of a runaway high-mass red-supergiant supernova progenitor, the morphology of its subsequent pulsar wind nebula is strongly affected by the wind of the defunct progenitor star pre-shaping the stellar surroundings throughout its entire past life. In particular, pulsar wind nebulae of obscured runaway massive stars harbour asymmetries as a function of the morphology of the progenitor’s wind-blown cavity, inducing projected asymmetric up–down synchrotron emission.
The zinc proteome of SARS-CoV-2
Authors: Andreini Claudia , Arnesano Fabio , Rosato Antonio
Published: June 2022

Zinc is an essential element for human health. Among its many functions, zinc(II) modulates the immune response to infections and, at high concentrations or in the presence of ionophores, inhibits the replication of various RNA viruses. Structural biology studies on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) revealed that zinc(II) is the most common metal ion that binds to viral proteins. However, the number of zinc(II)-binding sites identified by experimental methods is far from exhaustive, as metal ions may be lost during protein purification protocols. To better define the zinc(II)-binding proteome of coronavirus, we leveraged the wealth of deposited structural data and state-of-the-art bioinformatics methods. Through this in silico approach, 15 experimental zinc(II) sites were identified and a further 22 were predicted in Spike, open reading frame (ORF)3a/d, ORF8, and several nonstructural proteins, highlighting an essential role of zinc(II) in viral replication. Furthermore, the structural relationships between viral and eukaryotic sites (typically zinc fingers) indicate that SARS-CoV-2 can compete with human proteins for zinc(II) binding. Given the double-edged effect of zinc(II) ions, both essential and toxic to coronavirus, only the complete elucidation of the structural and regulatory zinc(II)-binding sites can guide selective antiviral strategies based on zinc supplementation.
Dual role of histone variant H3.3B in spermatogenesis: positive regulation of piRNA transcription and implication in X-chromosome inactivation
Authors: Fontaine Emeline , Papin Christophe , Martinez Guillaume , Le Gras Stéphanie , Nahed Roland Abi , Héry Patrick , Buchou Thierry , Ouararhni Khalid , Favier Bertrand , Gautier Thierry , Sabir Jamal S M , Gerard Matthieu , Bednar Jan , Arnoult Christophe , Dimitrov Stefan , Hamiche Ali
Published: June 2022

The histone variant H3.3 is encoded by two distinct genes, H3f3a and H3f3b, exhibiting identical amino-acid sequence. H3.3 is required for spermatogenesis, but the molecular mechanism of its spermatogenic function remains obscure. Here, we have studied the role of each one of H3.3A and H3.3B proteins in spermatogenesis. We have generated transgenic conditional knock-out/knock-in (cKO/KI) epitope-tagged FLAG-FLAG-HA-H3.3B (H3.3BHA) and FLAG-FLAG-HA-H3.3A (H3.3AHA) mouse lines. We show that H3.3B, but not H3.3A, is required for spermatogenesis and male fertility. Analysis of the molecular mechanism unveils that the absence of H3.3B led to alterations in the meiotic/post-meiotic transition. Genome-wide RNA-seq reveals that the depletion of H3.3B in meiotic cells is associated with increased expression of the whole sex X and Y chromosomes as well as of both RLTR10B and RLTR10B2 retrotransposons. In contrast, the absence of H3.3B resulted in down-regulation of the expression of piRNA clusters. ChIP-seq experiments uncover that RLTR10B and RLTR10B2 retrotransposons, the whole sex chromosomes and the piRNA clusters are markedly enriched of H3.3. Taken together, our data dissect the molecular mechanism of H3.3B functions during spermatogenesis and demonstrate that H3.3B, depending on its chromatin localization, is involved in either up-regulation or down-regulation of expression of defined large chromatin regions.
Peripheral expansion of myeloid-derived suppressor cells is related to disease activity and damage accrual in inflammatory myopathies
Authors: Torres-Ruiz Jiram , Absalón-Aguilar Abdiel , Reyes-Islas Juan Alberto , Cassiano-Quezada Fabiola , Mejía-Domínguez Nancy R , Pérez-Fragoso Alfredo , Maravillas-Montero José Luis , Núñez-Álvarez Carlos , Juárez-Vega Guillermo , Culebro-Bermejo Alejandro , Gómez-Martín Diana
Published: June 2022

Objective

To assess the proportion of myeloid-derived suppressor cells (MDSCs), their expression of arginase-1 and programmed cell death ligand 1 (PD-L1) and their relationship with the clinical phenotype of patients with idiopathic inflammatory myopathies (IIMs).

Methods

We recruited 37 IIM adult patients and 10 healthy donors in Mexico City. We evaluated their clinical features, the proportion of MDSCs and their expression of PD-L1 and arginase-1 by flow cytometry. Polymorphonuclear (PMN)-MDSCs were defined as CD33dim, CD11b+ and CD66b+ while monocytic (M)-MDSCs were CD33+, CD11b+, HLA-DR− and CD14+. Serum cytokines were analysed with a multiplex assay. We compared the quantitative variables with the Kruskal–Wallis and Mann–Whitney U tests and assessed correlations with Spearman’s ρ.

Results

Most patients had dermatomyositis [n = 30 (81.0%)]. IIM patients had a peripheral expansion of PMN-MDSCs and M-MDSCs with an enhanced expression of arginase-1 and PD-L1. Patients with active disease had a decreased percentage {median 1.75% [interquartile range (IQR) 0.31–5.50 vs 10.71 [3.16–15.58], P = 0.011} of M-MDSCs and a higher absolute number of PD-L1+ M-MDSCs [median 23.21 cells/mm3 (IQR 11.16–148.9) vs 5.95 (4.66–102.7), P = 0.046] with increased expression of PD-L1 [median 3136 arbitrary units (IQR 2258–4992) vs 1961 (1885–2335), P = 0.038]. PD-L1 expression in PMN-MDSCs correlated with the visual analogue scale of pulmonary disease activity (r = 0.34, P = 0.040) and damage (r = 0.36, P = 0.031), serum IL-5 (r = 0.55, P = 0.003), IL-6 (r = 0.46, P = 0.003), IL-8 (r = 0.53, P = 0.018), IL-10 (r = 0.48, P = 0.005) and GM-CSF (r = 0.48, P = 0.012). M-MDSCs negatively correlated with the skeletal Myositis Intention to Treat Index (r = −0.34, P = 0.038) and positively with IL-6 (r = 0.40, P = 0.045).

Conclusion

MDSCs expressing arginase-1 and PD-L1 are expanded in IIM and correlate with disease activity, damage accrual and serum cytokines.
Performance of a multisensor smart ring to evaluate sleep: in-lab and home-based evaluation of generalized and personalized algorithms
Authors: Grandner Michael A , Bromberg Zohar , Hadley Aaron , Morrell Zoe , Graf Arnulf , Hutchison Stephen , Freckleton Dustin
Published: June 2022

Study Objectives

Wearable sleep technology has rapidly expanded across the consumer market due to advances in technology and increased interest in personalized sleep assessment to improve health and mental performance. We tested the performance of a novel device, the Happy Ring, alongside other commercial wearables (Actiwatch 2, Fitbit Charge 4, Whoop 3.0, Oura Ring V2), against in-lab polysomnography (PSG) and at-home electroencephalography (EEG)-derived sleep monitoring device, the Dreem 2 Headband.

Methods

Thirty-six healthy adults with no diagnosed sleep disorders and no recent use of medications or substances known to affect sleep patterns were assessed across 77 nights. Subjects participated in a single night of in-lab PSG and two nights of at-home data collection. The Happy Ring includes sensors for skin conductance, movement, heart rate, and skin temperature. The Happy Ring utilized two machine-learning derived scoring algorithms: a “generalized” algorithm that applied broadly to all users, and a “personalized” algorithm that adapted to individual subjects’ data. Epoch-by-epoch analyses compared the wearable devices to in-lab PSG and to at-home EEG Headband.

Results

Compared to in-lab PSG, the “generalized” and “personalized” algorithms demonstrated good sensitivity (94% and 93%, respectively) and specificity (70% and 83%, respectively). The Happy Personalized model demonstrated a lower bias and more narrow limits of agreement across Bland-Altman measures.

Conclusion

The Happy Ring performed well at home and in the lab, especially regarding sleep/wake detection. The personalized algorithm demonstrated improved detection accuracy over the generalized approach and other devices, suggesting that adaptable, dynamic algorithms can enhance sleep detection accuracy.
A Systematic Review and Meta-analysis of Race/Ethnicity Reporting in Women’s Health Research [A54]
Authors: Michel Lindsey , Josama Pascale , Stern Rachel , Chudnoff Scott
Published: June 2022

INTRODUCTION:

Health disparities are well documented in the field of obstetrics and gynecology as highlighted by the current maternal mortality crisis. While research is pivotal to understanding the underlying causes of these disparities, minorities have traditionally been underrepresented in clinical studies. The objective of this study was to investigate trends in racial and ethnic reporting in women’s health research. Our secondary objective was to examine changes in reporting over the last decade.

METHODS:

A systematic review of original research articles from three high-impact obstetrics and gynecology journals (American Journal of Obstetrics & Gynecology (AJOG) Fertility & Sterility, and Obstetrics & Gynecology) was performed. Research articles were screened for the reporting of race/ethnicity and method of documenting data. Data were collected at 2- year timepoints, 2009 and 2019, for comparison.

RESULTS:

A total of 1,440 articles (AJOG n=514, Fertility & Sterility n=551, and Obstetrics & Gynecology n=375) were included and analyzed. Overall, race and ethnicity data were reported in 37.5% and 7.7% of research articles respectively. Only 2.2% of articles included both race and ethnicity data. There was a significant difference in the reporting of race (32.6% in 2009 vs. 54.8% in 2019, P<.05) and ethnicity (6.4% in 2009 vs. 10.1% in 2019, P<.05) data over the 10-year time span.

CONCLUSION:

The reporting of race/ethnicity is inconsistent and often lacking in women’s health literature. When reported, there is significant heterogeneity in how demographic data is documented. Although there have been some improvements in the last decade, standardized reporting could allow clinicians to be more informed of the generalizability of novel research findings.
New Opportunities for Expanding Rural Graduate Medical Education to Improve Rural Health Outcomes: Implications of the Consolidated Appropriations Act of 2021
Authors: Hawes Emily M. , Holmes Mark , Fraher Erin P. , Zamierowski Alyssa , Pauwels Judith , Sanner Louis A. , Rains Jacob , Page Cristen P.
Published: June 2022

Evidence shows that those living in rural communities experience consistently worse health outcomes than their urban and suburban counterparts. One proven strategy to address this disparity is to increase the physician supply in rural areas through graduate medical education (GME) training. However, rural hospitals have faced challenges developing training programs in these underserved areas, largely due to inadequate federal funding for rural GME. The Consolidated Appropriations Act of 2021 (CAA) contains multiple provisions that seek to address disparities in Medicare funding for rural GME, including funding for an increase in rural GME positions or “slots” (Section 126), expansion of rural training opportunities (Section 127), and relief for hospitals that have very low resident payments and/or caps (Section 131). In this Invited Commentary, the authors describe historical factors that have impeded the growth of training programs in rural areas, summarize the implications of each CAA provision for rural GME, and provide guidance for institutions seeking to avail themselves of the opportunities presented by the CAA. These policy changes create new opportunities for rural hospitals and partnering urban medical centers to bolster rural GME training, and consequently the physician workforce in underserved communities.
Distal Femur Growth Modification Surgery Is Associated With Higher Surgical Wound Complication Rate
Authors: Hsu Chen-Heng , Lee Wei-Chung , Kao Hsuan-Kai , Yang Wen E. , Chang Chia-Hsieh
Published: June 2022

Background:

Orthopaedic wound complications are often associated with extensive surgeries and patient medical conditions. However, we noticed wound complications in minor growth modification surgeries in children, including guided growth and epiphysiodesis. Herein, we report the complication rate and risk factors associated with pediatric growth modification surgeries.

Methods:

This retrospective study reviewed surgical wound complications in 622 pediatric orthopaedic patients who underwent growth modification surgeries (418 children) or osteotomies (204 children) in the lower extremities in a single center between 2007 and 2019. The grades II and III complications assessed using the modified Clavien-Dindo-Sink complication classification system were compared between growth modification and osteotomy. Risk factors for complications, including the type of surgery, age, body mass index, neuromuscular disease, operation time, surgical sites per patient, surgical location, and implant types, were analyzed using the logistic regression.

Results:

The complication rate was 6.9% per patient and 3.6% per surgical site (29 sites in 29 patients comprising 21 grade II and 8 grade III) in the growth modification group, which was >1.0% per patient and 0.6% per site in the osteotomy group (2 sites in 2 patients comprising 2 grade III infections; P=0.001). Among 418 patients with 797 surgical sites in the growth modification group, wound complications were associated with surgical location (5.2% at distal femur vs. 1.0% at proximal tibia, P=0.002) and implant type (0.5% using transphyseal screw vs. 4.3–10.5% using plates or staples, P=0.011).

Conclusion:

Surgical wound complication was associated with growth modification surgeries using plates or staples at the distal femur. Our results alert orthopaedic surgeons to this minor but unneglectable problem. Transphyseal screws may be the implant of choice for guided growth and epiphysiodesis at the distal femur in older children, considering the lower risks of wound complication.

Level of Evidence:

Level III, retrospective comparative study.
Use and safety of aprotinin in routine clinical practice
Authors: De Hert Stefan , Ouattara Alexandre , Royston David , van der Linden Jan , Zacharowski Kai
Published: June 2022

BACKGROUND

Aprotinin has been used to reduce blood loss and blood product transfusions in patients at high risk of major blood loss during cardiac surgery. Approval by the European Medicines Agency (EMA) for its current indication is limited to patients at high risk of major blood loss undergoing isolated coronary artery bypass graft surgery (iCABG).

OBJECTIVE

To report current real-world data on the use and certain endpoints related to the safety of aprotinin in adult patients.

DESIGN

The Nordic aprotinin patient registry (NAPaR) received data from 83 European centres in a noninterventional, postauthorisation safety study (PASS) performed at the request of the EMA.

SETTING

Cardiac surgical centres committed to enrolling patients in the NAPaR.

PATIENTS

Patients receiving aprotinin agreeing to participate.

INTERVENTION

The decision to administer aprotinin was made by the treating physicians.

MAIN OUTCOME MEASURES

Aprotinin safety endpoints were in-hospital death, thrombo-embolic events (TEEs), specifically stroke, renal impairment, re-exploration for bleeding/tamponade.

RESULTS

From 2016 to 2020, 5309 patients (male 71.5%; >75 years 18.9%) were treated with aprotinin; 1363 (25.7%) underwent iCABG and 3946 (74.3%) another procedure, including a surgical treatment for aortic dissection (n = 660, 16.7%); 54.5% of patients received the full-dose regimen. In-hospital mortality in iCABG patients was 1.3% (95% CI, 0.66 to 1.84%) vs. 8.3% (7.21 to 8.91%) in non-iCABG patients; incidence of TEEs and postoperative rise in creatinine level greater than 44 μmol l−1 2.3% (1.48 to 3.07%) and 2.7% (1.79 to 3.49%) vs. 7.2% (6.20 to 7.79%) and 15.5% (13.84 to 16.06%); patients undergoing re-exploration for bleeding 1.4% (0.71 to 1.93%) vs. 3.0% (2.39 to 3.44%). Twelve cases of hypersensitivity/anaphylactic reaction (0.2%) were reported as Adverse Drug Reactions.

CONCLUSION

The data in the NAPaR indicated that in this patient population, at high risk of death or blood loss undergoing cardiac surgery, including complex cardiac surgeries other than iCABG, the incidence of adverse events is in line with data from current literature, where aprotinin was not used.

TRIAL REGISTRATION

EU PAS register number: EUPAS11384.
Nurse Practitioners' Self-Efficacy and Behavior in Supporting Self-Management of Patients With a Progressive, Life-Threatening Illness and Their Relatives
Authors: Arslan Muzeyyen , van Dongen Sophie I. , Witkamp Erica , van Hooft Susanne M. , Billekens Pascalle , Kranenburg Leonieke W. , Stoevelaar Rik , van der Rijt Carin C.D. , van Dijk Monique , van der Heide Agnes , Rietjens Judith A.C.
Published: June 2022

This study aimed at investigating nurse practitioners' self-efficacy and behavior in supporting self-management of patients with a progressive, life-threatening illness and their relatives. We adapted an existing validated instrument for this purpose, amongst other things by adding a seventh subscale “attention for relatives,” and administered it in a nationwide, cross-sectional online survey among Dutch nurse practitioners. We analyzed associations between self-reported self-efficacy and behavior using Pearson correlations and paired sample t tests. Associations between self-efficacy and behavior with nurse practitioners' characteristics were examined using linear regression models. Most nurse practitioners (n = 327; 26% complete responses) were women (93%). Subscale and total scores for nurse practitioners' self-efficacy were moderately positively correlated with those for their behavior in self-management support. Subscale and total scores were statistically significantly higher for their self-efficacy than for their behavior. Increased work experience with patients with a progressive, life-threatening illness was associated with higher scores on self-efficacy and behavior in self-management support. We conclude that nurse practitioners are confident in their ability to support self-management; yet, they do not always use these competencies in practice.
Affordable Housing Specialists' Perceptions of Advance Care Planning Among Low-Income Older Adult Residents
Authors: Kimpel Christine C. , Jones Abigail C. , Ratcliff Amy C. , Maxwell Cathy A.
Published: June 2022

This preliminary qualitative study aimed to explore affordable housing specialists' perceptions of challenges and patterns of advance care planning behaviors among low-income older residents in affordable housing. Advance care planning rates among such residents are disproportionally lower than higher-income older adults. Individual telephone interviews were conducted with affordable housing specialists in a major urban area in the Southeastern United States (N = 5). Using thematic content analysis, 2 independent coders synthesized the 2 coding sets into a single codebook that was iteratively and individually reapplied to the transcripts. The Ecological Model of Active Living, a model that embeds individual behavior within a physical and social environment, was used to categorize prominent codes to visualize relationships among codes and create a cohesive, ecological picture of planning behavior in this population. Four themes emerged from the data and were plotted in an adapted ecological model. Residents' ongoing struggles despite obtaining housing prevent self-initiation and maintenance of advance care planning. Housing specialists possess the expertise and empathy to guide change efforts and provide advance care planning, but aid is required to ensure adequate resources to prevent role conflict and burnout. Recommendations for interprofessional collaboration, practice, policy, and research are discussed.
Elevated Blood Pressure and Stage 1 Hypertension in Pregnancy: A Review of the Literature
Authors: Wendel Michael P. , Bane Hunter , Frankowski Sara , Magann Everett F.
Published: June 2022

Importance

Maternal and perinatal morbidity/mortality is significantly increased in pregnancies complicated by hypertension. The definition of hypertension has recently changed with the addition of 2 categories: elevated blood pressure (BP) and stage 1 hypertension. Should these categories be considered during pregnancy?

Objective

The aim of this study was to analyze the impact of the new hypertensive categories of elevated BP and stage 1 hypertension on maternal/perinatal outcomes.

Methods

Literature search of PubMed, Web of Science, and CINAHL search was undertaken. Citations were limited to the past 20 years.

Results

Of the 333 articles identified, 26 articles were the basis of this review. In 2017, new guidelines on the diagnosis and management of hypertension were published. Prepregnancy hypertension was replaced by elevated BP (systolic BP 120–129 mm Hg and diastolic BP <80 mm Hg) and stage 1 hypertension (systolic BP 130–139 mm Hg and diastolic BP 80–89 mm Hg). The risk factors for elevated BP and stage 1 hypertension are similar to chronic hypertension (CHTN) risk factors, diagnosed by BP readings before pregnancy or before 20 weeks' gestation. Patients with elevated BP and stage 1 hypertension are at increased risk for hypertensive disorders of pregnancies compared with normal patients. Treatment strategies for elevated BP and stage 1 hypertension are uncertain. Before 2017, these patients would not have been considered hypertensive and no guidelines existed.

Conclusions

Elevated BP and stage 1 hypertension increase the number of women labeled with hypertension in pregnancy. These women are at increased risk for adverse perinatal and maternal outcomes. There are currently no firm guidelines on management during pregnancy.

Target Audience

Obstetricians and gynecologists, family medicine physicians

Learning Objectives

After completion of this article, the reader should be better able to evaluate the published literature regarding elevated BP and stage 1 hypertension and associated outcomes; identify additional risks of pregnancy associated with these conditions; and analyze current recommendations regarding management during pregnancy.
Breastfeeding: The Basics, the History, and Barriers in the Modern Day
Authors: Grundy Sara J. , Hardin Abigail , Kuller Jeffrey A. , Dotters-Katz Sarah
Published: June 2022

Importance

The scientific benefits of breastfeeding for the parent and baby are clear, but the goal is often simplified to “breast is best.” Patients' decisions to breastfeed are more nuanced than this approach implies, and it is essential for providers to understand other factors that contribute to this complex decision.

Objective

We reviewed the current literature of the health benefits of breastfeeding, local and global breastfeeding trends and current disparities, and the historical, political, and social factors that influence a patient’s decision to breastfeed.

Evidence Acquisition

Original research articles, review articles, and guidelines on breastfeeding were reviewed.

Results

Rates of breastfeeding have increased in the United States and globally after public health interventions, but significant disparities persist. Numerous factors influence a patient's decision to breastfeed including the medical benefits, formula marketing campaigns, historical connections to slavery and oppression, limited societal support for working parents, mental or physical health concerns, previous sexual abuse or trauma, gender identity, and others.

Conclusions and Relevance

Understanding both the medical importance of breastfeeding and the various other factors that influence a patient's decision or ability to breastfeed is essential for counseling patients before delivery. Providers have a responsibility to navigate this complex conversation with patients to empower them to make an informed decision that works for them.

Target Audience

Obstetricians and gynecologists, family physicians

Learning Objectives

After participating in this activity, the provider should be better able to explain the health benefits of breastfeeding for parent and infant; describe trends in breastfeeding rates and identify current disparities in breastfeeding within the United States and globally; and discuss the nuances of historical, political, social, and personal experience with a patient and its influence on their decision to breastfeed.
Clinical Experience With Non-invasive Prenatal Screening for Single-Gene Disorders
Authors: Mohan P. , Lemoine J. , Trotter C. , Rakova I. , Billings P. , Peacock S. , Kao C.-Y. , Wang Y. , Xia F. , Eng C. M. , Benn P.
Published: June 2022

(Abstracted from Ultrasound Obstet Gynecol 2022;59:33–39)

First described in 1997, the presence of cell-free fetal DNA in maternal plasma has been increasingly used in the last decade for cell-free DNA (cfDNA)–based noninvasive prenatal testing (NIPT) thanks to advances in molecular genetic technology. This method, now commonly used in the detection of fetal chromosomal abnormalities, can test for a variety of conditions.
Physician Perspectives on Acupuncture Use in the Pediatric Emergency Department
Authors: Jackson Jami , Esparham Anna , Dilts Jennifer , Boorigie Madeline , Randell Kimberly A.
Published: June 2022

Objectives

Acupuncture is a nonpharmalogical treatment modality that is used to treat pain. Prior research demonstrates that pediatric patients tolerate acupuncture well and patients may experience significant pain relief. The objectives of this study were to (1) explore the experiences of pediatric emergency department (ED) physicians as they used 2 acupuncture procedures, Battlefield Acupuncture and Four Gates procedures, and (2) describe factors impacting the feasibility of acupuncture implementation in the pediatric ED setting.

Methods

This qualitative study used individual semistructured interviews with pediatric emergency medicine physicians who had completed basic acupuncture training recruited using purposive sampling. Interviews were individually coded and analyzed using thematic analysis.

Results

Eight pediatric ED physicians participated in interviews. We identified multiple factors that promoted acupuncture use, multilevel barriers that impacted ED acupuncture implementation, offered multilevel solutions to overcome barriers to ED acupuncture implementation, and overall recommended continued use of ED acupuncture. Participants noted that education for patients, families, ED staff, and the general community may facilitate acupuncture implementation. To promote standardized and equitable access to acupuncture, participants recommended that all ED physicians in the division should be credentialed to provide acupuncture. In addition, participants recognized the benefits of an ED-specific electronic medical record documentation template and acupuncture toolbox including centralized acupuncture supplies, patient and family educational materials, and reference cards for physicians.

Conclusions

Participants overall had positive experiences with ED acupuncture. Although multilevel barriers to use of acupuncture were noted, these may be mitigated by several strategies suggested by participants. Future research is needed to further explore the potential impact of these strategies, as well as examine clinical outcomes of acupuncture implementation in the pediatric ED setting.
Pediatric Urgent Care Providers' Approach to Antibiotic Stewardship
Authors: Hamdy Rana F. , Nedved Amanda , Fung Melody , Fleming-Dutra Katherine E. , Liu Cindy M. , Obremskey Jill , Montalbano Amanda
Published: June 2022

Background

Outpatient antibiotic prescribing for acute respiratory conditions is highest in urgent care settings; however, this has not been studied among pediatric urgent cares. The objective of this study was to evaluate pediatric urgent care providers' perceptions of antibiotic stewardship.

Methods

Members of the Society for Pediatric Urgent Care were recruited via email to participate in a quality improvement antibiotic stewardship project. A preimplementation survey was sent to participants via email in March 2019 to evaluate perceptions on antibiotic stewardship. Descriptive statistics were used to analyze the survey responses.

Results

A total of 156 providers completed the survey; 83% were board-certified pediatricians. Almost all (98%) indicated that antibiotic stewardship interventions are important for optimizing antibiotic use in urgent care. More than half (53%) indicated that their urgent care provided guidelines for prescribing antibiotics for acute respiratory tract infections. Treating patients with an underlying complex medical condition was the most common reason (21%) providers would deviate from guidelines. The most commonly cited barriers to appropriate prescribing for acute respiratory infections were patient expectations (93%), psychosocial barriers (40%), lack of clear evidence-based recommendations (15%), and lack of access to guidelines on prescribing (15%).

Conclusions

Parental expectation of receiving antibiotics was viewed as the most common barrier to appropriate prescribing. These findings should be used to target directed interventions such as shared decision making and communication training to support appropriate antibiotic prescribing in pediatric urgent care.
Survival of Locally Advanced MSI-high Gastric Cancer Patients Treated With Perioperative Chemotherapy
Authors: Vos Elvira L. , Maron Steven B. , Krell Robert W. , Nakauchi Masaya , Fiasconaro Megan , Capanu Marinela , Walch Henry S. , Chatila Walid K. , Schultz Nikolaus , Ilson David H. , Janjigian Yelena Y. , Ku Geoffrey Y. , Yoon Sam S. , Coit Daniel G. , Vanderbilt Chad M. , Tang Laura H. , Strong Vivian E.
Published: June 2022

Objective:

To evaluate the efficacy of chemotherapy in patients with microsatellite instability (MSI)-high gastric cancer.

Background:

Although MSI-high gastric cancer is associated with a superior prognosis, recent studies question the benefit of perioperative chemotherapy in this population.

Methods:

Locally advanced gastric adenocarcinoma patients who either underwent surgery alone or also received neoadjuvant, perioperative, or adjuvant chemotherapy between 2000 and 2018 were eligible. MSI status, determined by next-generation sequencing or mismatch repair protein immunohistochemistry, was determined in 535 patients. Associations among MSI status, chemotherapy administration, overall survival (OS), disease-specific survival, and disease-free survival were assessed.

Results:

In 535 patients, 82 (15.3%) had an MSI-high tumor and ∼20% better OS, disease-specific survival, and disease-free survival. Grade 1 (90%–100%) pathological response to neoadjuvant chemotherapy was found in 0 of 40 (0%) MSI-high tumors versus 43 of 274 (16%) MSS. In the MSI-high group, the 3-year OS rate was 79% with chemotherapy versus 88% with surgery alone (P=0.48). In the MSS group, this was 61% versus 59%, respectively (P=0.96). After multivariable interaction analyses, patients with MSI-high tumors had superior survival compared with patients with MSS tumors whether given chemotherapy (hazard ratio=0.53, 95% confidence interval: 0.28–0.99) or treated with surgery alone (hazard ratio=0.15, 95% confidence interval: 0.02–1.17).

Conclusions:

MSI-high locally advanced gastric cancer was associated with superior survival compared with MSS overall, despite worse pathological chemotherapy response. In patients with MSI-high gastric cancer who received chemotherapy, the survival rate was ∼9% worse compared with surgery alone, but chemotherapy was not significantly associated with survival.
The Mycophenolate-based Immunosuppressive Regimen Is Associated With Increased Mortality in Kidney Transplant Patients With COVID-19
Authors: Requião-Moura Lúcio R. , Modelli de Andrade Luís Gustavo , de Sandes-Freitas Tainá Veras , Cristelli Marina Pontello , Viana Laila Almeida , Nakamura Mônica Rika , Garcia Valter Duro , Manfro Roberto Ceratti , Simão Denise Rodrigues , Almeida Ricardo Augusto Monteiro de Barros , Ferreira Gustavo Fernandes , Costa Kellen Micheline Alves Henrique , de Lima Paula Roberta , Pacheco-Silva Alvaro , Charpiot Ida Maria Maximina Fernandes , Deboni Luciane Mônica , Ferreira Teresa Cristina Alves , Mazzali Marilda , Calazans Carlos Alberto Chalabi , Oriá Reinaldo Barreto , Tedesco-Silva Hélio , Medina-Pestana José ,   on behalf of the COVID-19-KT Brazil Study Group*
Published: June 2022

Background.

The chronic use of immunosuppressive drugs is a key risk factor of death because of coronavirus disease 2019 (COVID-19) in kidney transplant recipients (KTRs), although no evident association between the class of immunosuppressive and outcomes has been observed. Thus, we aimed to compare COVID-19–associated outcomes among KTRs receiving 3 different immunosuppressive maintenance regimes.

Methods.

This study included data from 1833 KTRs with COVID-19 diagnosed between March 20 and April 21 extracted from the national registry before immunization. All patients were taking calcineurin inhibitor associated with mycophenolate acid (MPA, n = 1258), azathioprine (AZA, n = 389), or mammalian targets of rapamycin inhibitors (mTORi, n = 186). Outcomes within 30 and 90 d were assessed.

Results.

Compared with patients receiving MPA, the 30-d (79.9% versus 87.9% versus 89.2%; P < 0.0001) and 90-d (75% versus 83.5% versus 88.2%; P < 0.0001) unadjusted patient survivals were higher in those receiving AZA or mTORi, respectively. Using adjusted multivariable Cox regression, compared with patients receiving AZA, the use of MPA was associated with a higher risk of death within 30 d (adjusted hazard ratio [aHR], 1.70; 95% confidence interval [CI], 1.21-2.40; P = 0.003), which was not observed in patients using mTORi (aHR, 0.78; 95% CI, 0.45-1.35; P = 0.365). At 90 d, although higher risk of death was confirmed in patients receiving MPA (aHR, 1.46; 95% CI, 1.09-1.98; P = 0.013), a reduced risk was observed in patients receiving mTORi (aHR, 0.59; 95% CI, 0.35-0.97; P = 0.04) compared with AZA.

Conclusions.

This national cohort data suggest that, in KTRs receiving calcineurin inhibitor and diagnosed with COVID-19, the use of MPA was associated with higher risk of death, whereas mTORi use was associated with lower risk of death.
Resveratrol reduces p38 mitogen-activated protein kinase phosphorylation by activating Sirtuin 1 to alleviate cognitive dysfunction after traumatic brain injury in mice
Authors: Zhao Xing-Yuan , Yu Dong , Shi Xingjie , Hou Shiqiang , Teng Da
Published: June 2022

Traumatic brain injury (TBI) is characterized by neuronal loss and subsequent brain damage and can be accompanied by transient or permanent neurological dysfunction. The recovery of cognitive function after TBI is a challenge. This study aimed at investigating whether treatment with resveratrol (RSV) could prevent cognitive dysfunction after TBI in mice. TBI mouse model using weight drop-impact method. Male mice aged from 7 to 9 weeks were randomly divided into four groups: TBI group, TBI + vehicle group, TBI + RSV group, and sham-operated control group. The animals from the TBI + vehicle group and TBI + RSV group were intraperitoneally injected at 3 and 24 h post-TBI with placebo and RSV (3%, 5 ml/kg), respectively. Two days after TBI, the hippocampus of mice was extracted, and western blot analysis was performed for Sirtuin 1 (SIRT1), synaptophysin (SYP), p38 mitogen-activated protein kinase (MAPK), and P-p38 MAPK. Moreover, behavioral functions of TBI mice were evaluated by Y maze to determine RSV efficacy in preventing cognitive impairment in TBI. RSV increased the expression of SIRT1 protein, which in turn activated the phosphorylation of p38 MAPK. Taken together, our findings suggest that RSV exerts a strong beneficial effect on improving neurological function induced by TBI.
Investigation of the effects of high cervical spinal cord electrical stimulation on improving neurological dysfunction and its potential mechanism in rats with traumatic brain injury
Authors: Zhao Peng-Cheng , Huang Zhen-Shan , Xu Shao-Nian , Deng Peng-Cheng , Qian Feng , Shi Jian , Zhang Yong-Ming
Published: June 2022

To explore the effects of high cervical spinal cord electrical stimulation (cSCS) on the recovery of neurological function and its possible mechanism in rats with traumatic brain injury (TBI). 72 rats were randomly divided into: (1) a sham group; (2) a traumatic brain injury (TBI) group; (3) a TBI+cSCS group; (4) a LY294002+TBI+cSCS group. The degree of neurological dysfunction was evaluated by modified Neurological severity score (mNSS). The pathological changes of the brain tissue in the injured area were observed by HE staining, and the apoptosis of neuron cells were observed by TUNEL staining. The expressions of BDNF and VEGFmRNA were detected by polymerase chain reaction (PCR), and the expressions of p-AKT, AKT, Bcl-2, Bax and caspase-3 proteins were detected by western blot. Compared with that of the TBI and LY294002+TBI+cSCS groups, the mNSS of the TBI+cSCS group were significantly lower on day 3 and 7 (P <0.05). Compared with that in the TBI and LY294002+TBI+cSCS groups, the apoptosis of neuron cells in the TBI+cSCS group decreased significantly (P < 0.05). Compared with the TBI and LY294002+TBI+cSCS group, the expression of Bcl-2 protein increased and the expressions of Bax and Caspase-3 proteins decreased in the TBI+cSCS group (P < 0.05). Compared with that in the TBI and LY294002+TBI+cSCS groups, the intensity of p-Akt/Akt in the TBI+cSCS group increased (P < 0.05). We found that cSCS had a protective effect on neuron cells after craniocerebral injury and could improve neurological dysfunction in rats, the mechanism of which might be that cSCS made the PI3K/Akt pathway more active after TBI.
A network-based measure of functional diversity in food webs
Authors: Lin Wen-hsien , Lai Shu-mei , Davis Andrew J. , Liu Wei-chung , Jordán Ferenc
Published: June 2022

Biodiversity is measured from various perspectives. One of them, functional diversity, quantifies the heterogeneity in species traits and roles in an ecosystem. One important aspect of species roles is their interactions with other species, i.e. their network role. We therefore investigate here functional diversity from the network perspective. Species differ in their network positions in a food web, having different interaction patterns. We developed a measure for quantifying the diversity in species interaction patterns in a food web. We examined the relationship between interaction diversity and several global network properties for 92 food webs. Our results showed that high interaction diversity occurs in sparsely connected and less cohesive food webs. High interaction diversity also occurred in food webs with more clusters and high network modularity. We also quantified several conventional functional diversity indices and demonstrate that they show little or no correlation with interaction diversity. Our proposed diversity index therefore provides a measure complementary to current concepts of functional diversity.
Simon Hugh Piper Maddrell. 11 December 1937—10 September 2020
Authors: Skaer Helen , O'Donnell Michael J. , Dow Julian A. T.
Published: June 2022

Simon Maddrell transformed our understanding of how insects regulate their internal environments, a major determinant of their extraordinary success. Raised during wartime on his family's farm, Simon was a grammar school scholar at St Catharine's College, Cambridge, where he obtained the top first of his year in zoology. A keen sportsman, he combined his studies with half-Blues in table tennis and athletics. After a PhD under the supervision of Sir Vincent Wigglesworth FRS, he took a fellowship at Dalhousie University in Canada. He returned to Cambridge as a fellow of Gonville and Caius College, and took up a post in the AFRC Unit housed in the Department of Zoology. His academic work focused on the insect kidney, or Malpighian tubule. He unravelled details both of the mechanisms of secretion of fluids, ions and toxins, and of their control by the nervous system. His favoured organism was the blood-sucking ‘kissing bug’,
Rhodnius prolixus
, which demonstrated remarkable adaptations to handle massive (but irregular) blood meals. Later he also studied the classic genetic model insect
Drosophila melanogaster
, helping to lay the framework for combined physiological and genetic approaches in the same organism. Outside the lab, his massive energy and financial skills were potent influences on the Company of Biologists, a charity publishing scientific journals. Living increasingly in the family seat on the Isle of Man, he also brought his perfectionism to bear on daffodil shows and woodland tree planting. He is survived by his wife and four children.
Automated identification of chicken distress vocalizations using deep learning models
Authors: Mao Axiu , Giraudet Claire S. E. , Liu Kai , De Almeida Nolasco Inês , Xie Zhiqin , Xie Zhixun , Gao Yue , Theobald James , Bhatta Devaki , Stewart Rebecca , McElligott Alan G.
Published: June 2022

The annual global production of chickens exceeds 25 billion birds, which are often housed in very large groups, numbering thousands. Distress calling triggered by various sources of stress has been suggested as an ‘iceberg indicator’ of chicken welfare. However, to date, the identification of distress calls largely relies on manual annotation, which is very labour-intensive and time-consuming. Thus, a novel convolutional neural network-based model, light-VGG11, was developed to automatically identify chicken distress calls using recordings (3363 distress calls and 1973 natural barn sounds) collected on an intensive farm. The light-VGG11 was modified from VGG11 with significantly fewer parameters (9.3 million versus 128 million) and 55.88% faster detection speed while displaying comparable performance, i.e. precision (94.58%), recall (94.89%), F1-score (94.73%) and accuracy (95.07%), therefore more useful for model deployment in practice. To additionally improve light-VGG11's performance, we investigated the impacts of different data augmentation techniques (i.e. time masking, frequency masking, mixed spectrograms of the same class and Gaussian noise) and found that they could improve distress calls detection by up to 1.52%. Our distress call detection demonstration on continuous audio recordings, shows the potential for developing technologies to monitor the output of this call type in large, commercial chicken flocks.
Peeling dynamics of fluid membranes bridged by molecular bonds: moving or breaking
Authors: Kaurin Dimitri , Bal Pradeep K. , Arroyo Marino
Published: June 2022

Biological adhesion is a critical mechanical function of complex organisms. At the scale of cell–cell contacts, adhesion is remarkably tunable to enable both cohesion and malleability during development, homeostasis and disease. It is physically supported by transient and laterally mobile molecular bonds embedded in fluid membranes. Thus, unlike specific adhesion at solid–solid or solid–fluid interfaces, peeling at fluid–fluid interfaces can proceed by breaking bonds, by moving bonds or by a combination of both. How the additional degree of freedom provided by bond mobility changes the mechanics of peeling is not understood. To address this, we develop a theoretical model coupling diffusion, reactions and mechanics. Mobility and reaction rates determine distinct peeling regimes. In a diffusion-dominated Stefan-like regime, bond motion establishes self-stabilizing dynamics that increase the effective fracture energy. In a reaction-dominated regime, peeling proceeds by travelling fronts where marginal diffusion and unbinding control peeling speed. In a mixed reaction–diffusion regime, strengthening by bond motion competes with weakening by bond breaking in a force-dependent manner, defining the strength of the adhesion patch. In turn, patch strength depends on molecular properties such as bond stiffness, force sensitivity or crowding. We thus establish the physical rules enabling tunable cohesion in cellular tissues and in engineered biomimetic systems.