bluuebunny/crossref_metadata_2025 huggingface dataset:
To Align or Misalign?: Interpreting INGO-State Partnership in Cambodia
Authors: Wilks Mary-Collier
Published: January 2023

This article uses ethnographic and interview methods to compare two international nongovernmental organizations (INGOs) implementing public health programs in Cambodia. Both INGOs formally adopt the same policy, developing state partnership, but implement this policy very differently. One INGO successfully aligns the policy with on-the-ground practice, while the other organization is unable and unwilling to successfully cooperate with local state officials. I argue that previous research on international development organizations, policy convergence, and divergence in implementation needs to be expanded to analytically specify the process of policy alignment and misalignment. Drawing on the inhabited institutions perspective, I illustrate how global policies are made meaningful in intra- and inter-organizational interactions through a two-step process: (1) operationalization in which the broad policy is translated into specific programming and (2) implementation in which local actors do or do not align the policy with actual practice in Cambodia. This article offers a method for systematically theorizing policy alignment or misalignment with practice in international organizations.
NEW Soul in the neighborhood—reach and effectiveness of a dissemination and implementation feasibility study
Authors: Bernhart John A , Turner-McGrievy Gabrielle M , Wilson Mary J , Sentman Claudia , Wilcox Sara , Rudisill Caroline
Published: January 2023

Dissemination and implementation (D&I) studies of dietary interventions for African Americans are limited. Restaurants may be an innovative setting to deliver dietary interventions. Purpose: Assess weight loss, self-efficacy for healthy eating, diet quality, and quality of life in African Americans in two groups: virtual synchronous and virtual asynchronous. Guided by RE-AIM, the Nutritious Eating with Soul @ Rare Variety Café Feasibility study included nutrition education, accountability partners for support, and cooking demonstrations led by a community health worker and was delivered across two cohorts in a non-randomized design. The intervention was conducted over 12 consecutive weekly classes. Due to the COVID-19 pandemic, intervention delivery was online. African Americans between 18–65 years old with overweight/obesity, not currently following a plant-based diet or taking medications to control diabetes, and living in a southeastern city were recruited. Participants completed in-person weight assessments and online surveys at baseline and post-intervention. Linear mixed models analyzed changes in outcomes and differences in 3-month outcomes between groups. All models controlled for age and sex. Regarding Reach, 199 participants expressed interest, and 60 enrolled. Among the full sample, participants decreased body weight −2.6 ± 0.5 kg (p < .0001) and increased self-efficacy 1.6 ± 0.7 points (p = .03). No differences in 3-month outcomes between groups were observed. This D&I feasibility study successfully recruited participants during the COVID-19 pandemic and produced significant results. The successful online intervention delivery compared to in-person suggests the potential for greater D&I in vegan soul food restaurants. As restrictions are loosened, future studies will test in-person delivery.
Predicting the severity of traffic accidents on mountain freeways with dynamic traffic and weather data
Authors: Li Juan , Guo Fengxiang , Zhou Yanning , Yang Wenchen , Ni Dingan
Published: January 2023

Traffic accident severity prediction is essential for dynamic traffic safety management. To explore the factors influencing the severity of traffic accidents on mountain freeways and to predict the severity of traffic accidents, four models based on machine learning algorithms are constructed using support vector machine (SVM), decision tree classifier (DTC), Ada_SVM and Ada_DTC. In addition, random forest (RF) is used to calculate the importance degree of variables and the accident severity influences with high importance levels form the RF dataset. The results show that rainfall intensity, collision type, number of vehicles involved in the accident and road section type are important variables influencing accident severity. The RF feature selection method improves the classification performance of four machine learning algorithms, resulting in a 9.3%, 5.5%, 7.2% and 3.6% improvement in prediction accuracy for SVM, DTC, Ada_SVM and Ada_DTC, respectively. The combination of the Ada_SVM integrated algorithm and RF feature selection method has the best prediction performance, and it achieves 78.9% and 88.4% prediction precision and accuracy, respectively.
Glycyrrhizic acid improves tacrolimus‐induced renal injury by regulating autophagy
Authors: Cao Rui , Li Yakun , Hu Xiaofan , Qiu Yang , Li Shanglin , Xie Yanan , Xu Cong , Lu Chenqi , Chen Gang , Yang Jun
Published: January 2023

Tacrolimus (TAC)‐induced renal injury is detrimental to long‐term kidney function, but a treatment medication is not available. Glycyrrhizic acid (GA) is an active ingredient in licorice widely used to treat kidney disease. Thus, this study explored the mechanisms of renoprotection by GA on TAC‐induced renal injury. C57BL/6 mice were subjected daily to TAC or a combination of TAC and GA for 4 weeks, and then renal function, histopathology, and autophagy were assessed to examine the effect of GA on a renal injury. Next, Human kidney proximal tubular epithelial (HK‐2) cells were pretreated with GA for 2 h and then treated with TAC for 24 h. The effect of GA on TAC‐induced HK‐2 cell injury was assessed by measuring cell viability, apoptosis, autophagy, and lysosomes. Mice exposed to TAC and treated with GA had significantly greater improvements in renal function and tubulointerstitial fibrosis in comparison to mice not treated with GA. In addition, fibrosis‐related protein expression, including α‐smooth muscle actin and fibronectin, decreased after GA treatment. GA treatment also relieved autophagic clearance in TAC‐induced renal injury. Several in vitro studies found that TAC inhibited cell viability, autophagy, lysosomal acidification, and promoted apoptosis. However, these results were less pronounced with GA pretreatment. In addition, bafilomycin A1 (which inhibits lysosomal function) reduced the protective effect of GA, indicating that lysosomal function plays an important role in this effect. Our data suggest that GA improves lysosomal function and regulates autophagy to protect against TAC‐induced renal injury.
Neoadjuvant alectinib in locally advanced lung adenocarcinoma with anaplastic lymphoma kinase rearrangement: case series and literature review
Authors: Wang Zhaofeng , Wu Ranpu , Li Chuling , Cheng Kai , Di Yicheng , Lv Tangfeng , Liu Hongbing , Song Yong
Published: January 2023

In view of the success of targeted therapy in the field of advanced lung cancer, it is gradually pushed further to neoadjuvant therapy. Alectinib has been recommended for advanced anaplastic lymphoma kinase (ALK) + non-small cell lung cancer (NSCLC) in first-line therapy. Here, we report two cases of neoadjuvant alectinib in locally advanced lung adenocarcinoma with ALK rearrangement. Case 1 was a 64-year-old man with no history of smoking who was diagnosed with the clinical stage as IIIB, with ALK fusion-positive. Chest-enhanced computed tomography (CT) revealed marked regression and achieved partial response (PR) incorporated with grade 3 interstitial pneumonia after 44 days of alectinib neoadjuvant therapy. Interstitial pneumonia improved after methylprednisolone therapy, then thoracoscopic lobe resection with lymph node dissection was performed with blood loss. The pathological assessment was a pathologic complete response(pCR). Case 2 was a 66-year-old man who had a routine physical examination and then diagnosed with a clinical-stage IIIB by CT-guided percutaneous cutting needle biopsy (PCNB). Chemotherapy with 1 cycle of pemetrexed combined with nedaplatin was performed in the interval waiting for next-generation sequencing (NGS) results. NGS testing revealed an EML4-ALK fusion mutation. After 109 days of alectinib treatment, radiographic evaluation was classified as PR and then he underwent thoracoscopic upper lobectomy smoothly with pathological assessment as a major pathological response (MPR). To date, neoadjuvant alectinib has only been reported in a few cases in locally advanced lung adenocarcinoma with ALK-rearranged. Neoadjuvant alectinib may be feasible in locally advanced disease for complete resection. The duration and safety of neoadjuvant therapy with alectinib still need further study.
Examining Veterans’ Experiences With In Vitro Fertilization Provided Under P.L. 114–223
Authors: Mattocks Kristin M. , Marteeny Valerie , Walker Lorrie , Kroll-Desrosiers Aimee , Mengeling Michelle
Published: January 2023

Background:

Until recently, the Department of Veterans Affairs (VA) medical benefits package has expressly excluded in vitro fertilization (IVF) services for Veterans experiencing fertility problems. However, P.L. 114–223 (2016) allows VHA to provide Assisted Reproductive Technology, including IVF, to certain eligible Veterans. Little is known regarding Veterans’ experiences accessing IVF through VA Community Care contracts with IVF providers.

Objective:

To examine Veterans’ experiences with IVF services provided under the auspices of P.L. 114–223.

Research Design:

Telephone or video interviews were conducted with male and female Veterans and opposite-sex spouses of Veterans who had been approved for IVF. Interviews were recorded, transcribed, and analyzed using content analysis techniques. Major themes and representative quotes were derived from the analyses.

Results:

Ninety-six Veterans and 14 spouses participated in our interviews. Six major themes arose from these interviews, including (1) the need for improved communication regarding IVF benefits, (2) the need for expanded IVF benefits, (3) the lack of a comprehensive care coordination program, (4) poor access to IVF providers in some areas of the country, (5) special services needed for Veterans with spinal cord injuries, and (6) the IVF policy may be discriminatory in nature to single and LGBTQ Veterans.

Conclusions:

Many Veterans with service-connected conditions related to reproductive health have taken advantage of the IVF benefit, though limitations on these benefits have prevented other Veterans from taking advantage of the IVF benefit. Further attention needs to be paid to improving communication and coordination of IVF services with ongoing VA care and ensuring special populations, including those living in rural areas and Veterans with spinal cord injuries, have access to IVF services as needed.
High MRE11 Expression Level Predicts Poor Survival in Upper Tract Urothelial Carcinomas
Authors: Jhan Jhen-Hao , Ke Hung-Lung , Liang Peir-In , Hsu Wei-Chi , Lee Yi-Chen , Lin Hui-Hui , Wu Yi-Ru , Huang A-Mei , Lee Hsiang-Ying , Yeh Hsin-Chih , Wu Wen-Jeng , Li Ching-Chia , Li Wei-Ming
Published: January 2023

Upper tract urothelial carcinoma (UTUC) is an aggressive malignancy with characteristics of high metastasis and poor prognosis. There are some particularly different features of UTUC between the Asian and Western countries. Double-strand break repair protein MRE11 is a component of the MRN complex that is involved in the DNA repair pathway. Emerging studies have focused on the role of MRE11 in human malignancies with conflicting results. We aimed to establish the relationship between MRE11 expression and the oncological outcome of UTUC. This study retrospectively reviewed 150 patients who underwent radical nephroureterectomy with pathologically confirmed UTUC. Pathologic slides were reviewed, and clinical parameters were collected. An immunohistochemical study was performed, and the cytoplasmic and nuclear-staining results of UTUC were recorded. The expression of MRE11 was analyzed to identify correlations with various clinicopathological parameters, metastasis-free survival, and cancer-specific survival (CSS). MRE11 expression was significantly correlated with patients with a high pathologic stage (P=0.001), perineural invasion (P=0.015), and tumor necrosis (P=0.034). Upon univariate analysis, a high MRE11 expression was associated with poor metastasis-free survival (P=0.014, 95% CI 1.18, 4.38) and poor CSS (P=0.001, 95% CI 2.45, 27.75). Upon multivariable analysis, a high MRE11 expression was associated with poor CSS (P=0.019, 95% CI 1.28, 15.65). In summary, MRE11 expression could serve as a potential predictor of prognosis in patients with UTUC.
Successful use of differential target multiplexed spinal cord stimulation for chronic postsurgical abdominal pain
Authors: Tanaka Ryusuke , Shinohara Kenji , Hidai Yohei , Kiuchi Chiaki , Tanaka Satoshi , Kawamata Mikito , Sasao Junichi
Published: January 2023

Introduction:

Recent advances in stimulation techniques have improved the efficacy and expanded the applicability of spinal cord stimulation (SCS). Among these techniques, there are no reports on the efficacy of differential target multiplexed (DTM) SCS for chronic postsurgical pain (CPSP) after abdominal surgery. Therefore, we present the successful use of DTM SCS for CPSP after distal pancreatectomy.

Methods:

A 49-year-old man with hypertension and severe chronic low back pain presented with neuropathic CPSP involving the left abdomen in the area of a laparotomy incision. His pain was refractory to conservative treatment and was rated 10 on a numerical rating scale (NRS). He underwent permanent implantation of a pulse generator after a 14-day trial stimulation.

Results:

Chronic postsurgical pain was well controlled (NRS 1–2) at a 3-month follow-up with DTM SCS.

Conclusion:

Differential target multiplexed SCS can be a new treatment option for neuropathic CPSP that is resistant to conservative treatment. It is important to further examine the characteristics of CPSP and identify appropriate candidates for the successful use of DTM SCS.
Head and Neck Reconstruction With 2-Stage External Pectoralis Major Myocutaneous Flap Transfer
Authors: Moriguchi Kurumi , Kurita Tomoyuki , Fujii Takashi , Kawai Kenichiro , Kubo Tateki
Published: January 2023

Background

In head and neck surgery cases where skin is severely scarred or adhered to surrounding tissue, reconstruction can be difficult to perform using microsurgical tissue or conventional pedicled pectoralis major myocutaneous flap (PMMF) transfer given the risks, which include damage to major vessels when manipulating scarred skin. For such cases, we perform a 2-stage external PMMF transfer, whereby the PMMF is directly sutured to the defect over the neck skin (without manipulation the hardened skin), and the flap division is then performed secondarily.

Methods

A total of 30 patients who had histories of radiotherapy (60–70 Gy) and prior neck dissection received the 2-stage external PMMF transfer procedure. Indications for the flaps included pharyngeal fistula closure in 12 patients, reconstruction for mandibular necrosis after radiotherapy in 8 patients, salvage surgery for partial or total necrosis of the free flap in 4 patients, and simultaneous reconstruction after tumor excision in 6 patients. Two patients underwent a second external PMMF transfer from the contralateral side because of postoperative complications, yielding a total of 32 flap transfers.

Results

Twenty-nine flaps showed complete flap survival, whereas 3 had partial necrosis. Other complications, despite complete flap survival, included large fistulas requiring additional surgery for fistula closure (1 patient) and small fistulas that were closed without requiring reoperation (7 patients).

Conclusions

External PMMF transfer offers a safe, simple, and effective option in cases where free flap surgery is considered difficult or the risks associated with neck manipulation are high.
Induction in Pancreas Transplantation: T-cell Depletion Versus IL-2 Receptor Blockade
Authors: Aziz Fahad , Parajuli Sandesh , Kaufman Dixon , Odorico Jon , Mandelbrot Didier
Published: January 2023

Background.

There is limited data exist on relative outcomes with T-depletion versus IL-2 receptor (IL2R) blockade induction in pancreas transplantation.

Methods.

We analyzed all patients who underwent simultaneous pancreas-kidney or pancreas transplant alone at our institution between January 1, 2011, and December 31, 2019.

Results.

Of 417 pancreas transplant recipients, 291 received induction with a T-depleting agent and 126 received induction with an IL2R blocker. No difference was detected in pancreas allograft death-censored (P = 0.7) or uncensored (P = 0.5) survival. Although pancreas rejection was more common overall (P = 0.03), this difference was no longer present in recipients at low immunologic risk (P = 0.08). Cytomegalovirus and bacterial infections were significantly more common in the patients who received T-cell depleting agents for induction (21% versus 11%,P = 0.03; 34% versus 23%,P = 0.04, respectively). On multivariate analysis, history of pancreas rejection (Hazard ratio (HR) = 4.7,P = 0.0001; 95% Confidence interval (CI), 2.16-10.12) and higher calculated panel reactive antibodies (HR = 1.01,P = 0.04; 95% CI, 1.0002-1.02) were associated with increased risk of pancreas allograft failure, but choice of induction was not (HR = 0.64,P = 0.3; 95% CI, 0.27-1.51). Further, on multivariate analysis, Cytomegalovirus infection was associated with increased risk of pancreas allograft rejection (HR = 1.78,P = 0.01; 95% CI, 1.11-2.87), but choice of induction was not (HR = 0.84,P = 0.46; 95% CI, 0.54-1.32). Similarly, bacterial infection was associated with increased risk of patient death (HR = 2.94,P = 0.04; 95% CI, 1.03-8.32).

Conclusion.

Our data suggest that IL-2 receptor blockade may be a reasonable choice of induction for pancreas transplant recipients at low immunologic risk.
The contribution of parental health to the subsequent social assistance entry of the family with children– a nationwide register-linked birth cohort study in Finland
Authors: Hiilamo Aapo , Keski-Säntti Markus , Räsänen Sami , Niemelä Mika , Lallukka Tea , Ristikari Tiina
Published: January 2023

Aim

Our aim in this paper is to estimate the contribution of different parental specialised health care diagnoses to the subsequent risk of entry into the social assistance system for families with children in the period 1998–2013.

Methods

We used longitudinal population-level register data consisting of all children born in 1997 in Finland and their registered parents (54 960 one and two-parent families with 801 336 observations in the period 1998–2013). Diagnoses assigned in public specialised health care and social assistance records were derived from nationwide administrative registers. Measures of parental socioeconomic status and previous diagnoses and the birth weight of the child were adjusted for in regression models which estimated the association between parental diagnoses and entry into the social assistance system in the following year.

Results

Families with a parent somatic diagnosis had a risk ratio of 1.4 for social assistance entry in the subsequent year of the diagnosis though substantial variation by diagnosis category was detected. Parent psychiatric diagnoses were linked to a higher, 3.01-fold risk of social assistance entry. Covariate adjustment reduced these risk ratios to 1.2 and 2.1, respectively. Some 2.9 percent of all social assistance entries may be attributed to parental psychiatric diagnoses while somatic health records account for another 7.2 percent, making their total contribution over a tenth of all cases.

Conclusion

Parental specialised health care records was associated with a higher risk of social assistance need as more interventions to support financial management are required for parents with psychiatric diagnoses.

What is already known on this topic

Disruptive life events, such as work disability, unemployment or divorce, are associated with social assistance claims and usage in the general population

What this study adds

Parents’ diagnoses, particularly when due to psychiatric conditions, are associated with a higher risk of entry into the social assistance system

How this study might affect research, practice or policy

The findings are important in enabling us to recognise target groups and in designing interventions that aim to prevent families with children from falling into economic hardship
Cytokines in the Urine of AKI patients regulate TP53 and SIRT1 and can be used as biomarkers for the early detection of AKI
Authors: Erichsen Lars , Thimm Chantelle , Wruck Wasco , Kaierle Daniela , Schless Manon , Huthmann Laura , Dimski Thomas , Kindgen-Milles Detlef , Brandenburger Timo , Adjaye James
Published: January 2023

Acute kidney injury (AKI) is a major kidney disease with a poor clinical outcome. It is a common complication with an incidence of 10-15% of patients admitted to hospital. This rate even increases for patients who are admitted to the intensive care unit with an incidence of >50%. AKI is characterized by a rapid increase in serum creatinine, decrease in urine output, or both. Associated Symptoms include feeling sick or being sick, diarrhoea, dehydration, decreased urine output-although occasionally urine output remains normal, fluid retention-causing swelling in the legs or ankles, shortness of breath, fatigue and nausea. However, sometimes acute kidney injury causes no signs or symptoms and is detected by lab tests. Therefore, an urgent demand for non-invasive biomarkers for early detection of AKI are highly desirable. This might enable the prevention of the progression from AKI to CKD.

In this study, we analysed the secretome of urine of an AKI patient cohort employing a kidney-biomarker cytokine assay. Based on these results we suggest, ADIPOQ, EGF and SERPIN3A as potential biomarkers, which might be able to detect AKI as soon as 24 h post-surgery. For the later stages, common biomarkers for the detection of AKI in both male and female patients we suggest, VEGF, SERPIN3A, TNFSF12, ANPEP, CXCL1, REN, CLU and PLAU. These markers in combination might present a robust strategy to identify the development of AKI as early as 24h or 72h post-surgery. Furthermore, we evaluated the effect of patient and healthy urine on human podocyte cells. We conclude that cytokines in the urine of AKI patients trigger processes which are needed to repair the damaged nephron and activate TP53 and SIRT1 to maintain the balance between proliferation, angiogenesis, and cell cycle arrest. In conclusion, the Renin-Angiotensin pathway seems to have major implications.
Conflicts of Interest in Cardiology Journals
Authors: Smith- Manga Karsha M , Manga Atiba B , Piper Brian J
Published: January 2023

Background

Conflicts of interest are an ongoing concern in medical research. This takes place when the sponsor reports positive findings or promotes products over competitors because of their relationship and interaction with their industry sponsors. ThePhysicians Payment Sunshine Actmandates physicians who receive payments/compensation disclose their current and past relationships with different medical companies and the products they produce as an aim to manage conflicts of interest. In this quantitative bioethics study, we quantified financial conflicts of interest among cardiology journal authors and evaluated disparities in industry support among female and male physician-authors.

Methods

We reviewed 966 authors from 147 empirical research articles from two cardiology journals,Circulation, JCR 2021 Impact Factor (IF)= 29.7 andJournal of the American College of Cardiology(JACC), IF= 24.1, and one cardiovascular subspecialty journal,Catheterization and Cardiovascular Interventions(CCI), IF= 2.7. Articles published between January 1, 2020 and December 31, 2020 were reviewed. The database,OpenPayments.cms.gov(CMS-OP) was used to search author physician’s payments who reported receiving general payments, research payments, associated research funding, and ownership and investment interest between 2017 and 2019.

Results

A total of 19,529 payments totaled to 69,591,343.18 USD within the 36-month disclosure window. JACC accounted for 51.90%, Circulation 30.59% and CCI 17.51% of the total payment amounts. Male physician authors were more likely to receive industry sponsorship than their female counterparts (χ2(1)= 23.30;p<0.00001). The 139 male physicians with CMS-OP accounts made up 90.23% of payments, while females accounted for 9.77%.

Conclusion

In conclusion, cardiology journal authors received appreciable renumeration form industry. Female cardiology authors had lower representation in authorship and honorarium compared to their male colleagues. There were also occasional author disclosure discrepancies, where some authors failed to report their relationship with financial institutions, despite each author receiving greater than one million dollars (USD) over a 36-month window. The evidence from this investigation supports that financial conflicts of interest is an ongoing issue in cardiology journals.
Establishment of cell transcriptional identity during seed germination
Authors: Liew Lim Chee , You Yue , Oliva Marina , Peirats-Llobet Marta , Ng Sophia , Tamiru-Oli Muluneh , Berkowitz Oliver , Hong Uyen Vu Thuy , Haslem Asha , Stuart Tim , Ritchie Matthew E. , Bassel George W. , Lister Ryan , Whelan James , Gouil Quentin , Lewsey Mathew G.
Published: January 2023

Germination involves highly dynamic transcriptional programs as the cells of seeds reactivate and express the functions necessary to establish in the environment. Individual cell types have distinct roles within the embryo, so must therefore have cell-type specific gene expression and gene regulatory networks. We can better understand how the functions of different cell types are established and contribute to the embryo by determining how cell-type specific transcription begins and changes through germination. Here we describe a temporal analysis of the germinating Arabidopsis embryo at single-cell resolution. We define the highly dynamic cell-type specific patterns of gene expression and how these relate to changing cellular function as germination progresses. Underlying these are unique gene regulatory networks and transcription factor activity. We unexpectedly discover that most embryo cells transition through the same initial transcriptional state early in germination, after which cell-type specific gene expression is established. Furthermore, our analyses support previous findings that the earliest events leading to the induction of embryo growth take place in the vasculature. Overall, our study constitutes a general framework to characterise Arabidopsis cell states through embryo growth, allowing investigation of different genotypes and other plant species whose seed strategies may differ.
Effects of early life stress paired with adolescent alcohol consumption on two-bottle choice alcohol drinking behaviors in mice
Authors: Perry Thomas W. , Carvour Harrison M. , Reichert Amanda N. , Sneddon Elizabeth A. , Roemer Charlotte A.E.G. , Gao Ying Ying , Schuh Kristen M. , Shand Natalie A. , Quinn Jennifer J. , Radke Anna K.
Published: January 2023

Abstract

Background

In humans, early life stress (ELS) is associated with an increased risk for developing both alcohol use disorder (AUD) and post-traumatic stress disorder (PTSD). We previously used an infant footshock model that produces stress-enhanced fear learning (SEFL) in rats and mice and increases aversion-resistant alcohol drinking in rats to explore this shared predisposition. The goal of the current study was to extend this model of comorbid PTSD and AUD to male and female C57BL/6J mice.

Methods

Acute ELS was induced using 15 footshocks on postnatal day (PND) 17. In adulthood, alcohol drinking behavior was tested in one of three two-bottle choice drinking paradigms. In continuous access, mice were given 24 h access to 5% or 10% ethanol and water for five consecutive drinking sessions each. In limited access drinking in the dark, mice were given 2 h of access to 15% ethanol and water across 15 sessions 3 h into the dark cycle. In intermittent access, mice were presented with 20% ethanol and water Monday, Wednesday, and Friday, for four consecutive weeks. In a fifth week of intermittent access drinking, increasing concentrations of quinine (10 mg/L, 100 mg/L, and 200 mg/L) were added to the ethanol to test aversion-resistant drinking. Intermittent access drinking was tested with and without a period of adolescent drinking (PND 35).

Results

Infant footshock did not alter drinking in the continuous or limited access tasks. Adult consumption and preference were lower in the intermittent access task when adolescent drinking was included and there were ELS-induced differences in consumption of quinine-adulterated ethanol in females.

Conclusions

Our results demonstrate that infant footshock followed by a period of adolescent drinking is a viable model of comorbid PTSD and AUD in rats and mice.
Role of Gut Microbiome in Neoadjuvant Chemotherapy Response in Urothelial Carcinoma: A Multi-Institutional Prospective Cohort Evaluation
Authors: Bukavina Laura , Ginwala Rashida , Sindhani Mohit , Prunty Megan , Geynisman Daniel , Pooja Ghatalia , Valentine Henkel , Calaway Adam , Brown Jason R. , Correa Andres , Mishra Kirtishri , Pominville Raymond , Plimack Elizabeth , Kutikov Alexander , Ghannoum Mahmoud , ElShaer Mohammed , Retuerto Mauricio , Uzzo Robert , Ponsky Lee , Abbosh Philip H.
Published: January 2023

Treatment with neoadjuvant chemotherapy (NAC) in muscle invasive bladder cancer (MIBC) is associated with clinical benefit in urothelial carcinoma. While extensive research evaluating role of tumor mutational expression profiles and clinicopathologic factors into chemoresponse has been published, the role of gut microbiome (GM) in bladder cancer in chemoresponse has not been thoroughly evaluated. A working knowledge of the microbiome and its effect on all forms of cancer therapy in BC is critical. Here we examine gut microbiome of bladder cancer patients undergoing NAC. Overall, there was no significant difference in alpha and beta diversity by responder status. However, analysis of fecal microbiome samples showed that a higher abundance of Bacteroides within both institutional cohorts during NAC was associated with residual disease at the time of radical cystectomy regardless of chemotherapy regimen. Group community analysis revealed presence of favorable microbial subtypes in complete responders. Finally, fecal microbial composition outperformed clinical variables in prediction of complete response (AUC 0.88 vs AUC 0.50), however, no single microbial species could be regarded as a fully consistent biomarker. Microbiome-based community signature as compared to single microbial species is more likely to be associated as the link between bacterial composition and NAC response.
Gemini: Memory-efficient integration of hundreds of gene networks with high-order pooling
Authors: Woicik Addie , Zhang Mingxin , Xu Hanwen , Mostafavi Sara , Wang Sheng
Published: January 2023

Motivation

The exponential growth of genomic sequencing data has created ever-expanding repositories of gene networks. Unsupervised network integration methods are critical to learn informative representations for each gene, which are later used as features for downstream applications. However, these network integration methods must bescalableto account for the increasing number of networks androbustto an uneven distribution of network types within hundreds of gene networks.

Results

To address these needs, we present Gemini, a novel network integration method that uses memory-efficient high-order pooling to represent and weight each network according to its uniqueness. Gemini then mitigates the uneven distribution through mixing up existing networks to create many new networks. We find that Gemini leads to more than a 10% improvement in F1score, 14% improvement in micro-AUPRC, and 71% improvement in macro-AURPC for protein function prediction by integrating hundreds of networks from BioGRID, and that Gemini’s performance significantly improves when more networks are added to the input network collection, while the comparison approach’s performance deteriorates. Gemini thereby enables memory-efficient and informative network integration for large gene networks, and can be used to massively integrate and analyze networks in other domains.

Availability

Gemini can be accessed at:https://github.com/MinxZ/Gemini.

Contact

addiewc@cs.washington.edu,swang@cs.washington.edu
Spectroscopic insights into the mechanism of anammox hydrazine synthase
Authors: Versantvoort Wouter , Hienerwadel Rainer , Ferousi Christina , van der Velden Pieter , Berthomieu Catherine , van Niftrik Laura , Baymann Frauke
Published: January 2023

Anaerobic ammonium oxidizing bacteria make a living oxidizing ammonium with nitrite as electron acceptor, intermediates nitric oxide and hydrazine, and end product dinitrogen gas. Hydrazine is a biologically unique free intermediate in this metabolism, and is produced by the enzyme hydrazine synthase. Crystallization of ‘CandidatusKuenenia stuttgartiensis’ hydrazine synthase allowed for an initial hypothesis of its reaction mechanism. In this hypothesis, nitric oxide is first reduced to hydroxylamine after which hydroxylamine is condensed with ammonium to form hydrazine. Hydrazine synthase is a tetraheme cytochromec, containing two proposed active site hemes (γI & αI) in the γ- and α-subunit, respectively, connected by an intra-enzymatic tunnel. Here we combined the data from electrochemistry-induced Fourier transform infrared (FTIR) spectroscopy, EPR and optical spectroscopy to shed light on the redox properties and protein dynamics of hydrazine synthase in the context of its reaction mechanism. Redox titrations revealed two low potential low spin hemes with midpoint potentials of ∼-360 mV and ∼-310 mV for heme αII and γII, respectively. Heme γI showed redox transitions in the range of 0 mV, consisting of both low spin and high spin characteristics in optical and EPR spectroscopy. Electrochemistry-induced FTIR spectroscopy indicated an aspartic acid ligating a OH-/H2O at the heme γI axial site as a possible candidate for involvement in this mixed spin characteristic. Furthermore, EPR spectroscopy confirmed the ability of heme γI to bind NO in the reduced state. Heme αI exhibited a rhombic high spin signal, in line with its ligation by a proximal tyrosine observed in the crystal structure. Redox titrations down to −610 mV nor addition of dithionite resulted in the reduction of heme αI, indicating a very low midpoint potential for this heme.In vivochemistry at this heme αI, the candidate for the comproportionation of hydroxylamine and ammonium, is thus likely to be initiated solely on the oxidized heme, in contrast to previously reported DFT calculations. The reduction potentials of the γ-subunit hemes were in line with the proposed electron transfer of heme γII to heme γI for the reduction of NO to hydroxylamine (E0’ = − 30 mV).
Cdc73 protects Notch-induced T-cell leukemia cells from DNA damage and mitochondrial stress
Authors: Melnick Ashley F. , McCarter Anna C. , Liang Shannon , Liu Yiran , Wang Qing , Dean Nicole A. , Choe Elizabeth , Kunnath Nicholas , Bodanapu Geethika , Mullin Carea , Akter Fatema , Lin Karena , Magnuson Brian , Kumar Surinder , Lombard David B. , Muntean Andrew G. , Ljungman Mats , Sekiguchi JoAnn , Ryan Russell J.H. , Chiang Mark Y.
Published: January 2023

Activated Notch signaling is highly prevalent in T-cell acute lymphoblastic leukemia (T-ALL) but pan-Notch inhibitors were toxic in clinical trials. To find alternative ways to target Notch signals, we investigated Cell division cycle 73 (Cdc73), which is a Notch cofactor and component of transcriptional machinery, a potential target in T-ALL. While we confirmed previous work that CDC73 interacts with NOTCH1, we also found that the interaction in T-ALL was context-dependent and facilitated by the lymphoid transcription factor ETS1. Using mouse models, we showed that Cdc73 is important for Notch-induced T-cell development and T-ALL maintenance. Mechanistically, Cdc73, Ets1, and Notch intersect chromatin at promoters and enhancers to activate oncogenes and genes that are important for DNA repair and oxidative phosphorylation. Consistently,Cdc73deletion in T-ALL cells induced DNA damage and impaired mitochondrial function. Our data suggests that Cdc73 might promote a gene expression program that was eventually intersected by Notch to mitigate the genotoxic and metabolic stresses of elevated Notch signaling. We also provide mechanistic support for testing inhibitors of DNA repair, oxidative phosphorylation, and transcriptional machinery. Inhibiting pathways like Cdc73 that intersect with Notch at chromatin might constitute a strategy to weaken Notch signals without directly targeting the Notch complex.
Evidence for noisy oscillations of cAMP under nutritional stress condition in budding yeast
Authors: Colombo Sonia , Collini Maddalena , D’alfonso Laura , Chirico Giuseppe , Martegani Enzo
Published: January 2023

The Ras/cAMP/PKA pathway is one of the best studied signalling pathway in the budding yeast that regulates cellular responses to nutrients availability and stress. The cAMP levels and the PKA activity are also subjected to a strong negative feedback that operates either through the activity of the phosphodiesterase Pde1 and also on the amount of Ras2-GTP. We have previously made and simulated a dynamic model of the whole pathway and our results suggest the existence of stable oscillatory states that depend on the activity of the RasGEF (Cdc25) and RasGAP (Ira proteins) (Pescini et al. Biotechnol Adv 30, 99-107, 2012). Stochastic oscillations related to activity of the pathway were reported by looking at the nuclear localization of the trascription factors Msn2 and Msn4 (Gamedia-Torres et al. Curr Biol 17, 1044-9, 2007). In particular Medvedik et al. (PloS Biol 5, 2330-41, 2007) reported stable oscillations of the nuclear accumulation of Msn2 in condition of limited glucose availabiliy.

We were able to reproduce the periodic accumulation of Msn2-GFP protein in yeast cells under condition of limiting glucose, and we tried to detect also in the same condition oscillations of cAMP levels in single yeast cells. We used a specific Fluorescence Resonance Energy Transfer (FRET) sensor based on a fusion protein between CFP-EPAC-YFP expressed in yeast cells. The FRET between CFP and YFP is controlled by cAMP concentration. This sensor allows us to monitor changes in cAMP concentrations in single yeast cell for a relative long time and a peak of cAMP was normally detected after addition of glucose to derepressed cells (Colombo et al. Biochem Biophys Res Commun 487, 594-99, 2017). Using this method we were able to detect noisy oscillations of cAMP levels in single yeast cells under condition of nutritional stress caused by limiting glucose availability (0.1%). We used Spectral analysis to discriminate between true oscillations and random noise. The oscillations were characterized by period of about 4-5 min, close to that observed for Msn2-GFP oscillations.
EDA2R/NIK signaling promotes skeletal muscle atrophy linked to cancer cachexia
Authors: Nur Bilgic Sevval , Domaniku Aylin , Toledo Batu , Agca Samet , Weber Bahar Z. C. , Arabaci Dilsad H. , Ozornek Zeynep , Lause Pascale , Thissen Jean-Paul , Loumaye Audrey , Kir Serkan
Published: January 2023

Skeletal muscle atrophy is a hallmark of the cachexia syndrome that is associated with poor survival and reduced quality of life in cancer patients1. Muscle atrophy involves excessive protein catabolism and loss of muscle mass and strength2. An effective therapy against muscle wasting is lacking as mechanisms driving the atrophy process remain incompletely understood. Our gene expression analysis in muscle tissues revealed upregulation of Ectodysplasin A2 Receptor (EDA2R) in tumor-bearing mice and cachectic cancer patients. Here we show that activation of EDA2R signaling promotes skeletal muscle atrophy. Stimulation of primary myotubes with EDA2R ligand, EDA-A2, triggered pronounced cellular atrophy via inducing the expression of muscle atrophy-related genesAtrogin1andMuRF1. EDA-A2-driven myotube atrophy involved activation of the noncanonical NFκB pathway and depended on NIK kinase activity. While EDA-A2 overexpression induced muscle wasting in mice, the deletion of EDA2R or muscle NIK protected tumor-bearing mice from the loss of muscle mass and function. Tumor-induced Oncostatin M upregulated muscle EDA2R expression and muscle-specific Oncostatin M Receptor (OSMR) knockout mice were resistant to tumor-driven muscle wasting. Our results demonstrate that EDA2R/NIK signaling mediates cancer-associated muscle atrophy in an OSM/OSMR-dependent manner. Thus, therapeutic targeting of these pathways may be beneficial in preventing muscle loss.
Assessment of climate change mitigation readiness in the Kingdom of Bahrain
Authors: Alsabbagh Maha , Alnaser Waheeb Essa
Published: January 2023

Purpose

This study aims to assess readiness for climate change mitigation in the Kingdom of Bahrain.

Design/methodology/approach

Two stages were followed aiming at understanding the situation related to climate change mitigation in Bahrain and assessing the mitigation readiness. Baseline and mitigation scenarios for the period 2019–2040 were developed using the Low Emissions Analysis Platform software based on historical emissions and energy data for the period 1990–2018. Using the analytic hierarchy process, the mitigation readiness was assessed by 13 experts, and priority areas for mitigation action were identified.

Findings

CO2e emissions are projected to grow continuously. However, no explicit climate change strategy is in place yet. Mitigation is tackled implicitly through energy efficiency and renewable energy initiatives. These initiatives can make 23% reduction in CO2e emissions by 2040. Adopting additional measures is needed to achieve the recently set emission reduction target of 30% by 2035. The findings revealed potential areas for improving mitigation efforts in Bahrain. Priority areas for mitigation actions, as identified by experts, were mainly related to policy and governance. Focus needs to be paid to the social aspect of climate change mitigation.

Originality/value

Literature on mitigation readiness in developing countries is sparse. Knowledge of the requirements for climate change mitigation and assessment of the country’s performance can prioritize areas for improving mitigation action. Several lessons can be learnt from the case of Bahrain. In addition, the adopted methodology can be applied to other developing or Arab countries at local or institutional levels. However, its application to specific sectors may require adjustments.
Gaining resilience through transformative services in cause-related events: an interaction ritual chain perspective
Authors: Wong IpKin Anthony , Lin Xueying (Linda) , Lin Zhiwei (CJ) , Lin Yuxun (Emily)
Published: January 2023

Purpose

This study aims to unlock a ritual chain mechanism that promotes socio-mental (or socio-psychological) resilience. This study draws on interaction ritual chains theory and the concept of transformative service to answer the question of how people could be inspired toward an elevated level of group solidarity, emotional energy, morality and, thus, socio-mental resilience.

Design/methodology/approach

This study took a qualitative approach resting upon online reviews and observations from an augmented food festival about hot pot delicacies dedicated to medical workers fighting hard amid the early coronavirus outbreak.

Findings

The results of this study point to four primary ritual outcomes (e.g. emotional energy, group solidarity, symbols of relationships and standards of morality) along with a two-tier micro–macro socio-mental resilience sustainability paradigm.

Research limitations/implications

Empirical findings from this study could help operators to justify their transformative initiatives as means for customers to replenish their depleted physical and mental resources.

Originality/value

This inquiry presents new nuances to interaction ritual chains. This study also extends the transformative role of hospitality services to accentuate a linkage among individuals, communities and the society.
A system dynamic model for Indonesian petrochemical industry emission reduction
Authors: Sylvia Endang , Sunitiyoso Yos
Published: January 2023

Purpose

This paper aims to identify all variables and parameters related to business and emission within the petrochemical industry. The variables and parameters specified will be modeled into a system dynamic model that will be a baseline for the proposed best scenario(s) to address the business issue related to emission reduction in the petrochemical industry.

Design/methodology/approach

Literature review and stakeholder interviews were conducted to define the key factors contributing to the emission reduction of the petrochemical industry. The key factors are then developed into a system dynamic model to measure the quantitative impact of changes in those variables on emission and industry profitability.

Findings

This paper provides an analysis of system dynamic model. It suggests that process optimization can lead to a slight amount reduction in emissions. In contrast, a significant reduction shows in the simulation result of bio-based feedstock utilization and implementation of advanced technology. To sustain the emission reduction, strong commitment from stakeholders and support from the government will play an important role.

Research limitations/implications

This research is limited to problem analysis of the primary product (high-value chemical) of the petrochemical industry by only considering the changes in the key factors of emission reduction.

Practical implications

This paper includes implications for interventions that can be imposed to reduce emission while retaining the business profitability.

Originality/value

The contribution of this study is to find the best scenario that can boost emission reduction within Indonesia’s petrochemical industry.
Determinants of catastrophic household health expenditure in Nigeria
Authors: Opeloyeru Olaide Sekinat , Lawanson Akanni Olayinka
Published: January 2023

Purpose

The purpose of this paper is to examine the determinants of catastrophic household health expenditure in Nigeria, with particular focus on Out-of-Pocket (OOP) health expenditure. Payments for healthcare through OOP are the major means of channeling funds to healthcare providers in many developing countries including Nigeria. It has great consequence on household well-being, especially when it is difficult for household to meet up with spending on other necessity goods.

Design/methodology/approach

The demand for health theory provided the theoretical framework. The study used data from 2018/2019 Nigeria Living Standard Survey (NLSS) with catastrophic thresholds of 10 and 25%. A logistic regression model was used, while Pearson chi-squared test was used for models' goodness of fit.

Findings

Based on the obtained result using Pearson chi-squared, at 10% threshold of total non-food expenditure, the likelihood of experiencing catastrophic health expenditure increased with secondary education, for those without health insurance and for severely ill or injured by 1.48, 2.57 and 8.70, respectively. It fell for those who consulted patent medicine vendors/chemists for illness or injury by 0.63 compared to orthodox practitioners. Enhancement of post-secondary education and widening the coverage of the available social health insurance would minimise the financial burden on many households.

Originality/value

This paper fulfills the need to examine the determinants of catastrophic household health expenditure on two catastrophic thresholds and two forms of household expenditure.