bluuebunny/crossref_metadata_2025 huggingface dataset:
Nitrogen starvation causes lipid remodeling in Rhodotorula toruloides
Authors: Mishra Shekhar , Deewan Anshu , Zhao Huimin , Rao Christopher V.
Published: May 2024

Background

The oleaginous yeastRhodotorula toruloidesis a promising chassis organism for the biomanufacturing of value-added bioproducts. It can accumulate lipids at a high fraction of biomass. However, metabolic engineering efforts in this organism have progressed at a slower pace than those in more extensively studied yeasts. Few studies have investigated the lipid accumulation phenotype exhibited byR. toruloidesunder nitrogen limitation conditions. Consequently, there have been only a few studies exploiting the lipid metabolism for higher product titers.

Results

We performed a multi-omic investigation of the lipid accumulation phenotype under nitrogen limitation. Specifically, we performed comparative transcriptomic and lipidomic analysis of the oleaginous yeast under nitrogen-sufficient and nitrogen deficient conditions. Clustering analysis of transcriptomic data was used to identify the growth phase where nitrogen-deficient cultures diverged from the baseline conditions. Independently, lipidomic data was used to identify that lipid fractions shifted from mostly phospholipids to mostly storage lipids under the nitrogen-deficient phenotype. Through an integrative lens of transcriptomic and lipidomic analysis, we discovered thatR. toruloidesundergoes lipid remodeling during nitrogen limitation, wherein the pool of phospholipids gets remodeled to mostly storage lipids. We identify specific mRNAs and pathways that are strongly correlated with an increase in lipid levels, thus identifying putative targets for engineering greater lipid accumulation inR. toruloides. One surprising pathway identified was related to inositol phosphate metabolism, suggesting further inquiry into its role in lipid accumulation.

Conclusions

Integrative analysis identified the specific biosynthetic pathways that are differentially regulated during lipid remodeling. This insight into the mechanisms of lipid accumulation can lead to the success of future metabolic engineering strategies for overproduction of oleochemicals.
sEMG-based automatic characterization of swallowed materials
Authors: Hassan Eman A. , Khalifa Yassin , Morsy Ahmed A.
Published: May 2024

Monitoring of ingestive activities is critically important for managing the health and wellness of individuals with various health conditions, including the elderly, diabetics, and individuals seeking better weight control. Monitoring swallowing events can be an ideal surrogate for developing streamlined methods for effective monitoring and quantification of eating or drinking events. Swallowing is an essential process for maintaining life. This seemingly simple process is the result of coordinated actions of several muscles and nerves in a complex fashion. In this study, we introduce automated methods for the detection and quantification of various eating and drinking activities. Wireless surface electromyography (sEMG) was used to detect chewing and swallowing from sEMG signals obtained from the sternocleidomastoid muscle, in addition to signals obtained from a wrist-mounted IMU sensor. A total of 4675 swallows were collected from 55 participants in the study. Multiple methods were employed to estimate bolus volumes in the case of fluid intake, including regression and classification models. Among the tested models, neural networks-based regression achieved an R2 of 0.88 and a root mean squared error of 0.2 (minimum bolus volume was 10 ml). Convolutional neural networks-based classification (when considering each bolus volume as a separate class) achieved an accuracy of over 99% using random cross-validation and around 66% using cross-subject validation. Multiple classification methods were also used for solid bolus type detection, including SVM and decision trees (DT), which achieved an accuracy above 99% with random validation and above 94% in cross-subject validation. Finally, regression models with both random and cross-subject validation were used for estimating the solid bolus volume with an R2 value that approached 1 and root mean squared error values as low as 0.00037 (minimum solid bolus weight was 3 gm). These reported results lay the foundation for a cost-effective and non-invasive method for monitoring swallowing activities which can be extremely beneficial in managing various chronic health conditions, such as diabetes and obesity.
Effects of gender-affirming hormone therapy on body fat: a retrospective case‒control study in Chinese transwomen
Authors: Pei Qin , Song Yuwei , Huang Zhongwei , Yu Hongkun , Xu Hao , Ye Xunda , Gao Lvfen , Gong Jian , Tian Xiaoying
Published: May 2024

Background

There is insufficient research on how gender-affirming hormone therapy (GAHT) affects body fat modifications in transwomen from China. It is unclear whether hormone therapy affects the prevalence of obesity and blood lipid levels within this population. The current research aimed to assess how GAHT and treatment duration had an impact on the change in and redistribution of body fat in Chinese transwomen.

Methods

This study included 40 transwomen who had not received GAHT and 59 who had. Body fat, blood lipid, and blood glucose levels were measured. GAHT is mainly a pharmacologic (estrogen and anti-androgen) treatment. The study also stratified participants based on the duration of GAHT to assess its impact on body fat distribution. The duration of GAHT was within one year, one to two years, two to three years, or more than three years.

Results

After receiving GAHT, total body fat increased by 19.65%, and the percentage of body fat increased by 17.63%. The arm, corrected leg, and leg regions showed significant increases in fat content (+ 24.02%, + 50.69%, and + 41.47%, respectively) and percentage (+ 25.19%, + 34.90%, and + 30.39%, respectively). The total visceral fat content decreased (-37.49%). Based on the diagnostic standards for a body mass index ≥ 28 or total body fat percentage ≥ 25% or 30%, the chance of developing obesity did not change significantly. Blood glucose levels significantly increased (+ 12.31%). Total cholesterol levels (-10.45%) decreased significantly. Fat changes in those who received GAHT for one to two years were significantly different from those who did not receive GAHT.

Conclusion

After receiving GAHT, total body fat and regional fat increased in Chinese transwomen, and the body fat distribution changed from masculine to feminine, especially during the first two years. However, neither the increase in total body fat percentage nor the decrease in visceral fat content didn’t bring about significant changes in the incidence of obesity, nor did triglycerides or low-density lipoprotein-cholesterol.
Association between metabolic syndrome and kidney cancer risk: a prospective cohort study
Authors: Wang Lin , Du Han , Sheng Chao , Dai Hongji , Chen Kexin
Published: May 2024

Background

Kidney cancer has become known as a metabolic disease. However, there is limited evidence linking metabolic syndrome (MetS) with kidney cancer risk. This study aimed to investigate the association between MetS and its components and the risk of kidney cancer.

Methods

UK Biobank data was used in this study. MetS was defined as having three or more metabolic abnormalities, while pre-MetS was defined as the presence of one or two metabolic abnormalities. Hazard ratios (HRs) and 95% confidence intervals (CIs) for kidney cancer risk by MetS category were calculated using multivariable Cox proportional hazards models. Subgroup analyses were conducted for age, sex, BMI, smoking status and drinking status. The joint effects of MetS and genetic factors on kidney cancer risk were also analyzed.

Results

This study included 355,678 participants without cancer at recruitment. During a median follow-up of 11 years, 1203 participants developed kidney cancer. Compared to the metabolically healthy group, participants with pre-MetS (HR= 1.36, 95% CI: 1.06-1.74) or MetS (HR= 1. 70, 95% CI: 1.30-2.23) had a significantly greater risk of kidney cancer. This risk increased with the increasing number of MetS components (P for trend < 0.001). The combination of hypertension, dyslipidemia and central obesity contributed to the highest risk of kidney cancer (HR= 3.03, 95% CI: 1.91-4.80). Compared with participants with non-MetS and low genetic risk, those with MetS and high genetic risk had the highest risk of kidney cancer (HR= 1. 74, 95% CI: 1.41-2.14).

Conclusions

Both pre-MetS and MetS status were positively associated with kidney cancer risk. The risk associated with kidney cancer varied by combinations of MetS components. These findings may offer novel perspectives on the aetiology of kidney cancer and assist in designing primary prevention strategies.
A qualitative exploration of health care workers’ approaches to relational harm reduction in HIV primary care settings
Authors: Kay Emma Sophia , Creasy Stephanie L. , Townsend Jessica , Hawk Mary
Published: May 2024

Background

Structural harm reduction is an approach to care for people who use drugs (PWUD) that incorporates services and resources (e.g., naloxone, sterile syringes). As conceptualized in our previous research, harm reduction is also “relational,” encompassing a patient-provider relationship that is non-judgmental and respectful of patients’ autonomy. Little is known about health care workers’ (HCW) knowledge or attitudes towards harm reduction beyond structural strategies, whose availability and legality vary across geographical settings. To operationalize how relational harm reduction is both characterized and employed in HIV care settings, where nearly half of patients have a diagnosed substance use disorder, we qualitatively explored HCWs’ knowledge of and use of harm reduction via individual in-depth interviews.

Methods

Our study sample included three HIV clinics, one in Birmingham, Alabama (AL) and two in Pittsburgh, Pennsylvania (PA). We conducted individual interviews with n = 23 health care workers via Zoom, using a semi-structured interview guide to probe for questions around health care workers’ attitudes towards and experiences with providing care to PWH who use drugs and their knowledge of and attitudes towards relational and structural harm reduction. Data was analyzed in Dedoose using thematic analysis.

Results

Qualitative analyses revealed two primary themes, Continuum of Relational Harm Reduction in Practice and Limited Harm Reduction Training. Nearly all HCWs (n = 19, 83%) described a patient interaction or expressed a sentiment that corresponded with the principles of relational harm reduction. Yet, over half of participants (n = 14, 61%) used language to describe PWH who use drugs that was stigmatizing or described an interaction that was antithetical to the principles of relational harm reduction. Five HCWs, all from Birmingham, were unaware of the term ‘harm reduction.’ Few HCWs had any harm reduction training, with most learning about harm reduction from webinars/conferences or on the job.

Conclusion

Our findings suggest that relational harm reduction in HIV care settings is practiced along a continuum, and that a range of behaviors exist even within individual HCWs (e.g., used stigmatizing terms such as “addict” but also described patient interactions that reflected patients’ autonomy). Given that harm reduction is typically described as a structural approach, a broader definition of harm reduction that is not dependent on policy-dependent resources is needed.
Incidence of incisional hernia in patients undergoing cytoreductive surgery and hyperthermic intraperitoneal chemotherapy: an observational clinical study from a tertiary oncology referral care center in India
Authors: Ray Mukurdipi , Kumar Amit , Maranna Haraesh
Published: May 2024

Background

An incisional hernia (IH) after major abdominal surgery is an unwanted complication particularly following cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS and HIPEC). The frequency of IH among patients treated with CRS and HIPEC remains unexpectedly high in various studies. This study aimed to analyze the incidence, determine the factors contributing to the occurrence of IH, and develop methods to reduce the incidence of IH.

Methods

We retrospectively analyzed data from a prospectively maintained structured computerized comprehensive database of 360 patients who had undergone CRS and HIPEC after January 2013 and completed two years of follow-up before December 2023. All patients were followed for a minimum period of two years with physical examination and radiological imaging when required and the occurrence of IH was documented. We used SPSS software version 24 to analyze the data using appropriate statistical tests. We set a significance threshold of p < 0.05.

Results

Within two years of undergoing CRS and HIPEC, 25 patients (6.9%) out of 360 developed IH, indicating an annual incidence rate of 3.5%. The mean duration of hospitalization for the CRS/HIPEC procedure was 8.4 ± 4.13 days. Fifty-two (14.4%) patients experienced early post-operative surgical complications. The development of IH in our series was significantly associated with obesity (76% vs. 8.4%, P = 0.001), the occurrence of early post-operative surgical complications (48% vs. 12%, P = 0.001), mainly category III complications (44% vs. 7.1%), category IV complications (24% vs. 2.9%) according to Clavien-Dindo classification, post neoadjuvant chemotherapy status (72% vs. 87%, P = 0.045) and need for bowel anastomosis (32% vs. 11%, P = 0.002).

Conclusion

The lower incidence of IH following CRS and HIPEC in our patient cohort than in the literature can be attributed to a combination of factors, including the use of meticulous surgical techniques and the use of an abdominal binder postoperatively, particularly in obese patients.
Strengthening regional commitment to ensuring access to medical abortion medicines in WHO’s South-East Asia region: report of a participatory assessment and workshop
Authors: Upadhyay Meera Thapa , Fusire Terence , Loi Ulrika Rehnström , Sorhaindo Annik , Salahuddin Mohammed , Hossain Mohammed Ayub , Tshomo Tashi , Mulati Erna , Daisy Lovely , Anggraweni Dian Putri , Gultom Tumiur , Indrawati Fitri , Jenyfa Mariyam , Than Myint Myint , Bhattarai Bharat , Moonasinghe Loshan , Mathota Chaminda , Jitruknatee Anchalee , Cham Celeste , Ganatra Bela , Raina Neena
Published: May 2024

Background

In 2019, the World Health Organization identified improving access to safe abortion as an important priority toward improving sexual and reproductive health and rights and achieving Sustainable Development Goals. One strategy for addressing this priority is strengthening access to medicines for medical abortion. All 11 countries in the South-East Asia Region have some indications for legal abortion and permit post-abortion care. Therefore, strengthening access to medical abortion medicines is a reasonable strategy for improving access to safe abortion for the Region.

Methodology

We applied an adapted version of an existing World Health Organization landscape assessment protocol for the availability of medical abortion medicines at the country-level in the South-East Asia Region. We collected publicly available data on the existence of national health laws, policies, and standard treatment guidelines; inclusion of medical abortion medicines in the national essential medicines list; and marketing authorization status for medical abortion medicines for each country and verified by Ministries of health. The findings were once more presented, discussed and recommendations were formulated during regional technical consultation workshop. Each country teams participated in the process, and subsequently, the suggestions were validated by representatives from Ministries of Health..

Results

Few countries in the Region currently have national policies and guidelines for comprehensive safe abortion. However, either mifepristone-misoprostol in combination or misoprostol alone (for other indications) is included in national essential medicines lists in all countries except Indonesia and Sri Lanka. Few countries earmark specific public funds for procuring and distributing medical abortion commodities. In countries where abortion is legal, the private sector and NGOs support access to medical abortion information and medicines. Several countries only allow registered medical practitioners or specialists to administer medical abortion.

Conclusion

Following this rapid participatory assessment and technical consultation workshop, the World Health Organization South-East Asia Regional Technical Advisory and Sexual and Reproductive Health and Rights technical committee recommended priority actions for policy and advocacy, service delivery, and monitoring and evaluation, and indicated areas for support.
Clinico-demographic factors associated with the treatment response to cognitive behavioral therapy for insomnia
Authors: Hotchi Ayana , Yamadera Wataru , Iwashita Masayuki , Utsumi Tomohiro , Amagai Misato , Nakamura Sakumi , Suzuki Takako , Shigeta Masahiro
Published: May 2024

Background

Cognitive behavioral therapy for insomnia (CBT-I) is among the recommended non-pharmacological treatments for patients with insomnia. While there are multiple reports on the effects of CBT-I treatment, few studies evaluating the factors associated with the treatment response to CBT-I have been reported. The present study aimed to confirm the effects of CBT-I in patients with insomnia and to examine the clinico-demographic factors that can predict the outcomes of CBT-I in these patients.

Methods

Overall, 62 patients were included in the present study. To confirm the effectiveness of CBT-I, we compared the pre- and post-CBT-I therapy values of several sleep parameters. Furthermore, to identify the clinico-demographic factors that could be predictive of the treatment response to CBT-I, we performed generalized linear model (GLM) analysis.

Results

The values of several sleep parameters were significantly lower after treatment than at baseline. The results of the GLM analysis revealed that sex and occupation were significantly associated with the treatment response to CBT-I.

Conclusions

The present results suggest that several clinico-demographic factors should be considered in the treatment of patients with insomnia.
Metabolic landscape and pathogenic insights: a comprehensive analysis of high ovarian response in infertile women undergoing in vitro fertilization
Authors: Ruan Ling-Ling , Lv Xing-Yu , Hu Yu-Lin , Chen Ming-Xing , Jing-Tang  , Zhong Zhao-Hui , Bao Mei-Hua , Fu Li-Juan , Luo Xin , Yu Shao-Min , Wan Qi , Ding Yu-Bin
Published: May 2024

Background

In the realm of assisted reproduction, a subset of infertile patients demonstrates high ovarian response following controlled ovarian stimulation (COS), with approximately 29.7% facing the risk of Ovarian Hyperstimulation Syndrome (OHSS). Management of OHSS risk often necessitates embryo transfer cancellation, leading to delayed prospects of successful pregnancy and significant psychological distress. Regrettably, these patients have received limited research attention, particularly regarding their metabolic profile. In this study, we aim to utilize gas chromatography-mass spectrometry (GC-MS) to reveal these patients’ unique serum metabolic profiles and provide insights into the disease’s pathogenesis.

Methods

We categorized 145 infertile women into two main groups: the CON infertility group from tubal infertility patients and the Polycystic Ovary Syndrome (PCOS) infertility group. Within these groups, we further subdivided them into four categories: patients with normal ovarian response (CON-NOR group), patients with high ovarian response and at risk for OHSS (CON-HOR group) within the CON group, as well as patients with normal ovarian response (PCOS-NOR group) and patients with high ovarian response and at risk for OHSS (PCOS-HOR group) within the PCOS group. Serum metabolic profiles were analyzed using GC-MS. The risk criteria for OHSS were: the number of developing follicles > 20, peak Estradiol (E2) > 4000pg/mL, and Anti-Müllerian Hormone (AMH) levels > 4.5ng/mL.

Results

The serum metabolomics analysis revealed four different metabolites within the CON group and 14 within the PCOS group. Remarkably, 10-pentadecenoic acid emerged as a discernible risk metabolite for the CON-HOR, also found to be a differential metabolite between CON-NOR and PCOS groups. cysteine and 5-methoxytryptamine were also identified as risk metabolites for the PCOS-HOR. Furthermore, KEGG analysis unveiled significant enrichment of the aminoacyl-tRNA biosynthesis pathway among the metabolites differing between PCOS-NOR and PCOS-HOR.

Conclusion

Our study highlights significant metabolite differences between patients with normal ovarian response and those with high ovarian response and at risk for OHSS within both the tubal infertility control group and PCOS infertility group. Importantly, we observe metabolic similarities between patients with PCOS and those with a high ovarian response but without PCOS, suggesting potential parallels in their underlying causes.
Platelet-rich plasma (PRP) treatment of the ovaries significantly improves fertility parameters and reproductive outcomes in diminished ovarian reserve patients: a systematic review and meta-analysis
Authors: Éliás Máté , Kónya Márton , Kekk Zsófia , Turan Caner , das Virgens Isabel Pinto Amorim , Tóth Réka , Keszthelyi Márton , Hegyi Péter , Várbíró Szabolcs , Sipos Miklós
Published: May 2024

Introduction

The incidence of infertility caused by diminished ovarian reserve has become a significant problem worldwide. The beneficial effect of PRP treatment of the ovaries has already been described, but the high-level evidence of its effectiveness has not yet been proven.

Materials and methods

A systematic search was performed in five databases, until March 12th, 2024. Both randomized and non-randomized studies that compared PRP treatment of the ovaries to self-control among women with diminished ovarian reserve were eligible for inclusion.

Hormonal levels (Anti-Müllerian hormone (AMH), Follicle stimulating hormone (FSH), Luteinizing hormone (LH), Estradiol (E2), In-vitro fertilization parameters (Antral follicle count, oocyte, and embryo count), biochemical and spontaneous pregnancy and livebirth were measured.

Results

38 eligible studies were identified reporting on 2256 women. The level of AMH rised, the level of FSH decreased significantly after the PRP treatment. AMH 1 month MD 0.20 (n = 856, p > 0.001, 95% CI: [0.12;0.28]), 2 months MD 0.26 (n = 910, p = 0.013, 95% CI: [0.07;0.44]), 3 months MD 0.36 (n = 881, p = 0.002,95% CI: [0.20;0.52]). FSH 1 month MD -10.20 (n = 796, p > 0.039, 95% CI: [-19.80;-0.61]), 2 months MD -7.02 (n = 910, p = 0.017, 95% CI: [-12.48; -1.57]), 3 months MD -8.87 (n = 809, p = 0.010, 95% CI: [-14.19; -3.55]).

The antral follicle count elevated significantly MD 1.60 (n = 1418, p =  < 0.001, 95% CI: [0.92; 2.27]). Significant improvement was observed in the number of retrieved oocytes MD 0.81 (n = 802, p = 0.002, 95% CI: [0.36; 1.26]), and embryos created MD 0.91 (n = 616, p = 0.001, 95% CI: [0.45;1.36]).

The incidence of spontaneous pregnancy following PRP treatment showed a rate with a proportion of 0.07 (n = 1370, 95% CI: 0.04–0.12), the rate of biochemical pregnancy was 0.18 (n = 1800, 95% CI: 0.15–0.22), livebirth was 0.11 (n = 1482, 95% CI: 0.07–0.15).

Conclusions

Our meta-analysis showed that based on protocolized analysis of the widest scientific literature search to date, containing predominantly observational studies, PRP treatment resulted in a statistically significant improvement in the main fertility parameters of diminished ovarian reserve women. Further multicenter, randomized trials, with large patient numbers and a longer follow-up period are needed to certify our results and develop the most effective treatment protocol.

Graphical Abstract
The burden of radiation exposure in congenital heart disease: the Italian cohort profile and bioresource collection in HARMONIC project
Authors: Campolo Jonica , Annoni Giuseppe , Vignati Gabriele , Peretti Alessio , Papa Marco , Colombo Paola Enrica , Muti Gaia , Parolini Marina , Borghini Andrea , Giaccardi Marzia , Ait-Alì Lamia , Picano Eugenio , Andreassi Maria Grazia
Published: May 2024

Background

The European-funded Health Effects of Cardiac Fluoroscopy and Modern Radiotherapy in Pediatrics (HARMONIC) project aims to improve knowledge on the effects of medical exposure to ionizing radiation (IR) received during childhood. One of its objectives is to build a consolidated European cohort of pediatric patients who have undergone cardiac catheterization (Cath) procedures, with the goal of enhancing the assessment of long-term radiation-associated cancer risk.

The purpose of our study is to provide a detailed description of the Italian cohort contributing to the HARMONIC project, including an analysis of cumulative IR exposure, reduction trend over the years and an overview of the prospective collection of biological samples for research in this vulnerable population.

Methods

In a single-center retrospective cohort study, a total of 584 patients (323 males) with a median age of 6 (2–13) years, referred at the Pediatric Cardiology in Niguarda Hospital from January 2015 to October 2023, were included. Biological specimens from a subset of 60 patients were prospectively collected for biobanking at baseline, immediately post-procedure and after 12 months.

Results

Two hundred fifty-nine (44%) patients were under 1 year old at their first procedure. The median KAP/weight was 0.09 Gy·cm2/kg (IQR: 0.03–0.20), and the median fluoroscopy time was 8.10 min (IQR: 4.00–16.25). KAP/weight ratio showed a positive correlation with the fluoroscopy time (Spearman’s rho = 0.679, p < 0.001). Significant dose reduction was observed either after implementation of an upgraded technology system and a radiation training among staff. The Italian cohort includes 1858 different types of specimens for Harmonic biobank, including blood, plasma, serum, clot, cell pellet/lymphocytes, saliva.

Conclusions

In the Italian Harmonic cohort, radiation dose in cardiac catheterization varies by age and procedure type. An institution’s radiological protection strategy has contributed to a reduction in radiation dose over time. Biological samples provide a valuable resource for future research, offering an opportunity to identify potential early biomarkers for health surveillance and personalized risk assessment.
Protocolized reduction of non-resuscitation fluids versus usual care in septic shock patients (REDUSE): a randomized multicentre feasibility trial
Authors: Lindén Anja , Spångfors M. , Olsen M. H. , Fisher J. , Lilja G. , Sjövall F. , Jungner M. , Lengquist M. , Kander T. , Samuelsson L. , Johansson J. , Palmnäs E. , Undén J. , Oras J. , Cronhjort M. , Chew M. , Linder A. , Lipcsey M. , Nielsen N. , Jakobsen J. C. , Bentzer P. ,   for the REDUSE Trial Group, Fisher Jane , Nelderup Maria , Hassel Lisa , Johnsson Eva , Claesson Camilla , Lybeck Anna , Schrey Susann , Andersson Linda K. , Holmström Sandra , Larsson Marina , Bramell Katarina , Aspholm Karin , Olne Karin , Larsson Hanna , Lipscey Miklos , Skåne Region , Nielsen Niklas
Published: May 2024

Background/purpose

Non-resuscitation fluids constitute the majority of fluid administered for septic shock patients in the intensive care unit (ICU). This multicentre, randomized, feasibility trial was conducted to test the hypothesis that a restrictive protocol targeting non-resuscitation fluids reduces the overall volume administered compared with usual care.

Methods

Adults with septic shock in six Swedish ICUs were randomized within 12 h of ICU admission to receive either protocolized reduction of non-resuscitation fluids or usual care. The primary outcome was the total volume of fluid administered within three days of inclusion.

Results

Median (IQR) total volume of fluid in the first three days, was 6008 ml (interquartile range [IQR] 3960–8123) in the restrictive fluid group (n = 44), and 9765 ml (IQR 6804–12,401) in the control group (n = 48); corresponding to a Hodges–Lehmann median difference of 3560 ml [95% confidence interval 1614–5302]; p < 0.001). Outcome data on all-cause mortality, days alive and free of mechanical ventilation and acute kidney injury or ischemic events in the ICU within 90 days of inclusion were recorded in 98/98 (100%), 95/98 (98%) and 95/98 (98%) of participants respectively. Cognition and health-related quality of life at six months were recorded in 39/52 (75%) and 41/52 (79%) of surviving participants, respectively. Ninety out of 134 patients (67%) of eligible patients were randomized, and 15/98 (15%) of the participants experienced at least one protocol violation.

Conclusion

Protocolized reduction of non-resuscitation fluids in patients with septic shock resulted in a large decrease in fluid administration compared with usual care. A trial using this design to test if reducing non-resuscitation fluids improves outcomes is feasible.

Trial registration

Clinicaltrials.gov, NCT05249088, 18 February 2022. https://clinicaltrials.gov/ct2/show/NCT05249088
Breaking down causes, consequences, and mediating effects of telomere length variation on human health
Authors: Moix Samuel , Sadler Marie C , Kutalik Zoltán , Auwerx Chiara
Published: May 2024

Background

Telomeres form repeated DNA sequences at the ends of chromosomes, which shorten with each cell division. Yet, factors modulating telomere attrition and the health consequences thereof are not fully understood. To address this, we leveraged data from 326,363 unrelated UK Biobank participants of European ancestry.

Results

Using linear regression and bidirectional univariable and multivariable Mendelian randomization (MR), we elucidate the relationships between leukocyte telomere length (LTL) and 142 complex traits, including diseases, biomarkers, and lifestyle factors. We confirm that telomeres shorten with age and show a stronger decline in males than in females, with these factors contributing to the majority of the 5.4% of LTL variance explained by the phenome. MR reveals 23 traits modulating LTL. Smoking cessation and high educational attainment associate with longer LTL, while weekly alcohol intake, body mass index, urate levels, and female reproductive events, such as childbirth, associate with shorter LTL. We also identify 24 traits affected by LTL, with risk for cardiovascular, pulmonary, and some autoimmune diseases being increased by short LTL, while longer LTL increased risk for other autoimmune conditions and cancers. Through multivariable MR, we show that LTL may partially mediate the impact of educational attainment, body mass index, and female age at childbirth on proxied lifespan.

Conclusions

Our study sheds light on the modulators, consequences, and the mediatory role of telomeres, portraying an intricate relationship between LTL, diseases, lifestyle, and socio-economic factors.
HSP70 positively regulates translation by interacting with the IRES and stabilizes the viral structural proteins VP1 and VP3 to facilitate duck hepatitis A virus type 1 replication
Authors: Jiang Yurui , Xu Chenxia , Cheng Anchun , Wang Mingshu , Zhang Wei , Zhao Xinxin , Yang Qiao , Wu Ying , Zhang Shaqiu , Tian Bin , Huang Juan , Ou Xumin , Sun Di , He Yu , Wu Zhen , Zhu Dekang , Jia Renyong , Chen Shun , Liu Mafeng
Published: May 2024

The maintenance of viral protein homeostasis depends on the interaction between host cell proteins and viral proteins. As a molecular chaperone, heat shock protein 70 (HSP70) has been shown to play an important role in viral infection. Our results showed that HSP70 can affect translation, replication, assembly, and release during the life cycle of duck hepatitis A virus type 1 (DHAV-1). We demonstrated that HSP70 can regulate viral translation by interacting with the DHAV-1 internal ribosome entry site (IRES). In addition, HSP70 interacts with the viral capsid proteins VP1 and VP3 and promotes their stability by inhibiting proteasomal degradation, thereby facilitating the assembly of DHAV-1 virions. This study demonstrates the specific role of HSP70 in regulating DHAV-1 replication, which are helpful for understanding the pathogenesis of DHAV-1 infection and provide additional information about the role of HSP70 in infection by different kinds of picornaviruses, as well as the interaction between picornaviruses and host cells.
Generalizations of Levinson-type inequalities via new Green functions and Hermite interpolating polynomial
Authors: Rasheed Awais , Khan Khuram Ali , Pečarić Josip , Pečarić Ðilda
Published: May 2024

In this study, Levinson-type inequalities for the class of n-convex ($n \geq 3$
n
≥
3
) functions are generalized using new Green functions and the Hermite interpolating polynomial involving two types of data points. Some estimations for novel functionals are derived using f-divergence. Furthermore, different inequalities involving Shannon entropies are presented.
A fuel consumption-based method for developing local-specific CO2 emission rate database using open-source big data
Authors: Li Linheng , Wang Can , Gan Jing , Zhang Dapeng
Published: May 2024

Emission data collection has always been a significant burden and challenge for Chinese counties to develop a CO2 emission inventory. This paper proposed a fuel consumption-based method to develop a local-specific CO2 emission rate database for Chinese counties using only open-source big data. Localized vehicle fuel consumption data is obtained through natural language processing (NLP) algorithm and large language model (LLM). The emission rates derived by our proposed method are consistent with field test results in literature. Besides, the CO2 emission estimation results using local-specific traffic activity data indicate that our method could effectively improve the accuracy of vehicle emission assessment. Compared with conventional method, the novel approach proposed in this paper can provide a pathway for convenient, universal, and cost-saving assessment for local scale CO2 emission rates. With this method, it is possible to formulate a local-specific CO2 emission database in various Chinese counties using only open-access big data.
Immune checkpoint inhibitors and pericardial disease: a systematic review
Authors: Mudra Sarah E. , Rayes Danny L. , Agrawal Ankit , Kumar Ashwin K. , Li Jason Z. , Njus Meredith , McGowan Kevin , Kalam Kazi A. , Charalampous Charalompos , Schleicher Mary , Majid Muhammad , Syed Alvena , Yesilyaprak Abdullah , Klein Allan L.
Published: May 2024

Introduction

Despite the growing use of immune checkpoint inhibitors (ICI) in cancer treatment, data regarding ICI-associated pericardial disease are primarily derived from case reports and case series. ICI related pericardial disease can be difficult to diagnose and is associated with significant morbidity. We conducted a systematic review to further characterize the epidemiology, clinical presentation, and outcomes of this patient population.

Methods

A search of four databases resulted in 31 studies meeting inclusion criteria. Patients > 18 years old who presented with ICI mediated pericardial disease were included. Intervention was medical + surgical therapy and outcomes were development of cardiac tamponade, morbidity, and mortality.

Results

Thirty- eight patients across 31 cases were included. Patients were majority male (72%) with a median age of 63. Common symptoms included dyspnea (59%) and chest pain (32%), with 41% presenting with cardiac tamponade. Lung cancer (81%) was the most prevalent, and nivolumab (61%) and pembrolizumab (34%) were the most used ICIs. Pericardiocentesis was performed in 68% of patients, and 92% experienced symptom improvement upon ICI cessation. Overall mortality was 16%.

Discussion

This study provides the most comprehensive analysis of ICI-mediated pericardial disease to date. Patients affected were most commonly male with lung cancer treated with either Nivolumab or Pembrolizumab. Diagnosis may be challenging in the setting of occult presentation with normal EKG and physical exam as well as delayed onset from therapy initiation. ICI-associated pericardial disease demonstrates high morbidity and mortality, as evidenced by a majority of patients requiring pericardiocentesis.
Effect of Maitland mobilization versus deep cervical flexors muscles training on proprioception in adults with chronic mechanical neck pain: a randomized controlled trial
Authors: Amin Fatma Sadeek , Abdel-Aal Nabil Mahmoud , El Shater Ban Saleh
Published: May 2024

Objective

To examine the effect of adding Maitland mobilization (MM) versus deep cervical flexors muscles training (DCFMT) to conventional physical therapy (CPT) on proprioception in adults with chronic mechanical neck pain (CMNP).

Materials and methods

A randomized controlled study was carried out at the outpatient clinics of physical therapy at Cairo and Suez universities. Sixty participants (27 males, 33 females) with CMNP were randomized into 3 equivalent groups. Group I received MM plus CPT, group II received DCFMT in addition to CPT, and group III received CPT only. All individuals were given three sessions a week for 4 weeks. The primary outcomes were proprioception (CROM), and pain (VAS). The secondary outcomes were cranio-vertebral angle (CVA), and upper cervical angle (C0–C2). Outcomes were evaluated at baseline and following 4 weeks of treatment.

Results

Following 4 weeks of treatment, the DCFMT group showed statistically significant improvement to the MM group as well as the CPT group in all outcome measures (p > 0.05). Also, the MM group was remarkably better than the CPT group in all measured outcomes (p > 0.05). The mean signed difference (M±SD) post-treatment within the group of VAS were 6.87 ± 1.26, 7.15 ± 1.38, and 7.20 ± 1.39 cm for MM, DCFMT, and CPT groups respectively. The (M±SD) of CVA were 42.61 ± 4.36, 42.24 ± 3.64, and 42.32 ± 4.81 degrees for MM, DCFMT, and CPT groups respectively. The (M±SD) of C0–C2 were 24.25 ± 2.98, 23.37 ± 1.94, and 24.95 ± 3.01 degrees for MM, DCFMT, and CPT groups respectively. The (M±SD) of flexion JPE to target were 3.62 ± 0.91, 2.86 ± 0.77, and 4.35 ± 0.91 degrees for MM, DCFMT, and CPT groups respectively. The (M±SD) of flexion JPE to neutral were 3.96 ± 0.78, 2.66 ± 1.03, and 5.23 ± 1.52 degrees for MM, DCFMT, and CPT groups respectively.

Conclusion

Adding MM and DCFMT to CPT revealed significant enhancement, favoring DCFMT, on proprioception, pain, cranio-vertebral angle (CVA), upper cervical angle (C0–C2), and intensity than CPT alone in adults with CMNP.

Trial registration

Pan African Clinical Trails Registry with a registration No. PACTR202211651838599 on the 3rd of November 2022.
Investigation of the epidemiology, pathogenicity and immunogenicity of Bordetella bronchiseptica isolated from cats and dogs in China from 2021 to 2023
Authors: Shang Qinghua , Gao Wenhui , Zhang Xiangting , Zhao Jianqing , Wu Ying , Li Haoqi , Zhou Ming , Fu Zhen F. , Zhang Chengguang , Zhao Ling
Published: May 2024

Bordetella bronchiseptica (Bb) is recognized as a leading cause of respiratory diseases in dogs and cats. However, epidemiological data on Bb in dogs and cats in China are still limited, and there is no commercially available vaccine. Live vaccines containing Bb that are widely used abroad are generally effective but can establish latency and potentially reactivate to cause illness in some immunodeficient vaccinated recipients, raising safety concerns. In this study, 34 canine-derived and two feline-derived Bb strains were isolated from 1809 canine and 113 feline nasopharyngeal swab samples collected from eight provinces in China from 2021 to 2023. The PCR results showed that the percentage of positive Bb was 22.94% (441/1922), and more than 90% of the Bb isolates had four virulence factor-encoding genes (VFGs), namely, fhaB, prn, betA and dnt. All the isolated strains displayed a multidrug-resistant phenotype. The virulence of 10 Bb strains isolated from dogs with respiratory symptoms was tested in mice, and we found that eight isolates were highly virulent. Furthermore, the eight Bb isolates with high virulence were inactivated and intramuscularly injected into mice, and three Bb strains (WH1218, WH1203 and WH1224) with the best protective efficacy were selected. Dogs immunized with these three strains exhibited strong protection against challenge with the Bb field strain WH1218. Ultimately, the WH1218 strain with the greatest protection in dogs was selected as the vaccine candidate. Dogs and cats that received a vaccine containing 109 CFU of the inactivated WH1218 strain showed complete protection against challenge with the Bb field strain WH1218. This study revealed that Bb is an important pathogen that causes respiratory diseases in domestic dogs and cats in China, and all the isolates exhibited multidrug resistance. The present work contributes to the current understanding of the prevalence, antimicrobial resistance, and virulence genes of Bb in domestic dogs and cats. Additionally, our results suggest that the WH1218 strain is a promising candidate safe and efficacious inactivated Bb vaccine.
Significance of QTc Interval in Chronic Hypoparathyroidism and its Correlates
Authors: Namjoshi Preeti , Saha Soma , Sharma Vibhav , Kalaivani Mani , Narang Rajiv , Goswami Ravinder
Published: May 2024

Context

Hypocalcemia predisposes patients with chronic hypoparathyroidism (cHypoPT) to an increased risk of QTc prolongation and life-threatening arrhythmias. Information on clinical and biochemical correlates of QTc in cHypoPT is limited.

Objective

To assess the significance of QTc interval in chronic hypoparathyroidism and its correlates.

Methods

This was an observational cohort study at a tertiary care center. Eighty-eight nonsurgical patients with cHypoPT (mean age 44.1 ± 15.4 years, 45 males) were assessed for QTc interval and its possible correlates including arrhythmic symptoms (palpitation/giddiness/syncope), serum total calcium, phosphate, 25(OH)D, and intact parathyroid hormone.

Results

The mean QTc in the HypoPT cohort was 428 ± 34 ms with 13.6% having prolonged QTc. There was a significant inverse correlation between QTc interval and serum total calcium measured on the same day (r = −0.43, P < .001). The mean serum total calcium was significantly lower in patients with prolonged QTc (7.05 ± 1.94 vs 8.49 ± 1.01 mg/dL, P = .02). Of patients with cHypoPT 21.6% had arrhythmic symptoms. They had significantly higher mean QTc (P = .02) and also tended to have lower mean serum total calcium during follow-up (P = .06). In multivariable regression, female gender, higher current age, higher body mass index, and low serum total calcium showed significant association with prolonged QTc. For every mg/dL decrease in serum total calcium, QTc increased by 13 ms. Receiver operating characteristic analysis revealed serum total calcium at cut-off of 8.3 mg/dL discriminated prolonged QTc with area under the curve being 0.72 (95% CI 0.51, 0.93).

Conclusion

One-fifth of patients with cHypoPT had arrhythmic symptoms and a significant proportion had prolonged QTc. This highlights the need for close monitoring of patients with cHypoPT for arrhythmic symptoms and QTc prolongation. The serum total calcium should be maintained to at least 8.3 mg/dL to minimize the risk of potentially life-threatening arrhythmia in cHypoPT.
Hybrid Baihua 白話 as a Third Space: East Asian Anticolonial Writing in Modern China
Authors: Lin Chai , Dongmei Li
Published: May 2024

After the colonial invasion of East Asia, numerous Koreans, Vietnamese, and Japanese went to China and began a long anticolonial struggle. During this period, they chose to write and communicate in a fourth language, Baihua 白話, for anticolonial purposes. While writing in Baihua, they brought the grammar and word order of their mother tongues into Baihua, creating “Korean-style vernacular Chinese,” “Japanese-style vernacular Chinese,” and “Vietnamese-style vernacular Chinese.” The emergence of these hybridized Baihuas is related to the anticolonialists’ cooperation with the Kuomintang government, the oppression of the Kuomintang government, and the authority of Literary Sinitic and Baihua. As a form of subversion of and resistance to the authority of Literary Sinitic and Baihua, the hybrid Baihuas thus constructed served as an anticolonial third space.
Acute Vigorous Exercise Decreases Subsequent Nonexercise Physical Activity and Body Temperature Linked to Weight Gain
Authors: FUNABASHI DAISUKE , DOBASHI SHOHEI , SAMESHIMA KAZUKI , SAGAYAMA HIROYUKI , NISHIJIMA TAKESHI , MATSUI TAKASHI
Published: May 2024

Purpose

Exercise benefits the body and mind, but its weight loss effect is less than generally expected. Although this phenomenon is likely due to an exercise intensity–dependent decrease in non-exercise physical activity (NEPA), resulting in a decrease in non-exercise activity thermogenesis, the underlying mechanisms and effects of exercise intensity remain unknown. Here we show that acute vigorous exercise decreases subsequent NEPA and body temperature (BT) in association with body weight gain.

Methods

Adult male C57BL/6J mice were categorized into three groups: sedentary, moderate exercise, and vigorous exercise, with exercise groups undergoing a 30-min treadmill session. Using an intraperitoneally implanted activity monitor, NEPA and BT were monitored for 2 d before and 3 d after exercise. The daily synchrony between NEPA and BT was evaluated using a cross-correlation function. Plasma corticosterone was also detected 6 and 24 h after exercise.

Results

Notably, only the vigorous exercise group exhibited a decline in both NEPA and BT, resulting in body weight gain the following day, despite no observed changes in food intake. Furthermore, vigorous exercise induces a distinct delay in the daily dynamics of NEPA compared with BT. A positive correlation was observed between plasma corticosterone levels and changes in NEPA levels before and after exercise across all exercise groups.

Conclusions

Our findings provide evidence for vigorous exercise–specific reduction in subsequent NEPA, BT, and their synchrony linked to weight gain, likely due to the disturbed circadian rhythm of corticosterone. This is an initial investigation redefining the significance of exercise intensity in beneficial effects beyond the energy expenditure of the exercise itself.
Neoplatonic and Gnostic Resonances in the Martyrdom of Cyprian of Athenais Eudocia
Authors: Dendrinos Markos , Griva Anna
Published: May 2024

Aelia Eudocia Augusta (formerly Athenais), wife of the emperor Theodosius II, lives at the borderline between the ancient and the Christian world and writes one of the most distinctive poetic texts of Byzantine literature. In the Martyrdom of Cyprian, written in Homeric language, the Saint's past, when he was a magician and initiated into a multitude of Greek mysteries, is presented in an original and remarkable way. Within this text, the resonance of philosophical ideas originating from  Neoplatonism and Gnosticism is of particular interest. This article attempts to highlight these resonances in order to open a research dialogue regarding the complex network of ideas and the coexistence of different worldviews in early Byzantium.