bluuebunny/crossref_metadata_2025 huggingface dataset:
Recurrent colon cancer in a patient with Muir–Torre syndrome: a case report
Authors: Rivkin Angeline C , Bystrom Philip , Lin Amy Y , Chaudhry Vivek
Published: February 2024

Muir–Torre syndrome (MTS) is a rare subtype of hereditary nonpolyposis colorectal cancer syndrome caused by a defect in DNA mismatch repair leading to microsatellite instability. It is characterized by the presence of at least one sebaceous gland tumor and one internal malignancy, most commonly colorectal and endometrial tumors. These patients have a high propensity for tumorigenesis, and while strict screening protocols are in place, there are only two cases that describe the management approach to recurrent colon cancer. Here, we present a case of recurrent colorectal cancer in a patient with MTS, and describe how it was managed at our facility by a multidisciplinary team.
A nearby polluted white dwarf with a 6.2 h spin period
Authors: Farihi Jay , Robert Akshay , Walters Nikolay
Published: February 2024

This letter reports the first detection of a periodic light curve whose modulation is unambiguously due to rotation in a polluted white dwarf. TESS observations of WD 2138−332, at a distance of 16.1 pc, reveal a 0.39 per cent amplitude modulation with a 6.19 h period. While this rotation is relatively rapid for isolated white dwarfs, it falls within the range of spin periods common to those with detectable magnetic fields, where WD 2138−332 is notably both metal-rich and weakly magnetic. Within the local 20 pc volume of white dwarfs, multisector TESS data find no significant periodicities among the remaining 16 polluted objects (five of which are also magnetic), whereas six of 23 magnetic and metal-free targets have light curves consistent with rotation periods between 0.7 and 35 h (three of which are new discoveries). This indicates the variable light curve of WD 2138−332 is primarily a result of magnetism, as opposed to an inhomogeneous distribution of metals. From 13 magnetic and metallic degenerates with acceptable TESS data, a single detection of periodicity suggests that polluted white dwarfs are not rotating as rapidly as their magnetic counterparts, and planet ingestion is thus unlikely to be a significant channel for rapid rotation.
Census for the rest-frame optical and UV morphologies of galaxies at z = 4–10: First phase of inside-out galaxy formation
Authors: Ono Yoshiaki , Harikane Yuichi , Ouchi Masami , Nakajima Kimihiko , Isobe Yuki , Shibuya Takatoshi , Nakane Minami , Umeda Hiroya , Xu Yi , Zhang Yechi
Published: February 2024

We present the rest-frame optical and UV surface brightness (SB) profiles for 149 galaxies with Mopt < −19.4 mag at z = 4–10 (29 of which are spectroscopically confirmed with JWST NIRSpec), securing high signal-to-noise ratios of 10–135 with deep JWST NIRCam 1–$5\, \mu$m images obtained by the CEERS survey. We derive morphologies of our high-z galaxies, carefully evaluating the systematics of SB profile measurements with Monte Carlo simulations as well as the impacts of a) AGNs, b) multiple clumps including galaxy mergers, c) spatial resolution differences with previous HST studies, and d) strong emission lines, e.g., Hα and [O iii], on optical morphologies with medium-band F410M images. Conducting Sérsic profile fitting for our high-z galaxy SBs with GALFIT, we obtain effective radius ranges for optical re,opt and UV re,UV wavelengths of re, opt = 0.05–1.6 kpc and re,UV = 0.03–1.7 kpc that are consistent with previous results within large scatters in the size–luminosity relations. However, we find that the effective radius ratio, re,opt$/$re,UV, is almost unity, $1.01^{+0.35}_{-0.22}$, over z = 4–10 with no signatures of past inside-out star formation such as found at z ∼ 0–2. There are no spatial offsets exceeding 3σ between the optical and UV morphology centers in cases of no mergers, indicative of major star-forming activity only being found near mass centers of galaxies at z ≳ 4 probably experiencing the first phase of inside-out galaxy formation.
Sexual dysfunction in women with primary Sjögren’s syndrome: a systematic review and meta-analysis
Authors: Hsu Chia-Wen , Lee Jian Tao , Koo Malcolm
Published: February 2024

Introduction

Primary Sjögren’s syndrome (pSS) is an inflammatory autoimmune condition affecting the exocrine glands, which can adversely affect the sexual activities of women with pSS.

Objectives

The study sought to evaluate the performance of the Female Sexual Function Index (FSFI) score in women with pSS regarding desire, arousal, orgasm, lubrication, satisfaction, and pain compared with those of healthy individuals.

Methods

A systematic review was conducted by examining studies published up to May 2023 using Embase, Web of Science, Scopus, and PubMed with the search terms “sexual” and “Sjögren’s syndrome.”

Results

Out of the 228 articles retrieved, 9 met the criteria for inclusion in this systematic review. Six of these studies were cross-sectional, involving 229 women with pSS and 303 control subjects. Results from the meta-analysis showed that women with pSS had significantly lower scores in all 6 FSFI subdomains and the total FSFI score compared with healthy individuals. Lubrication showed the largest decrease, followed by pain. In addition, women with pSS exhibited significantly higher standardized mean differences in depression and in anxiety, as assessed by the Hospital Anxiety and Depression Scale, when compared with control subjects.

Conclusion

This updated meta-analysis underscores the importance of assessing genitourinary atrophy, disease-related psychological changes, and dyspareunia in women with pSS. It also emphasizes the need for customized therapeutic approaches to address these sexual dysfunctions effectively.
Adapting to stress: The effects of hibernation and hibernacula temperature on the hepatic transcriptome of Rhinolophus pusillus
Authors: Wang Ying , Wang Xufan , Chen Yu , Du Jianying , Xiao Yanhong , Guo Dongge , Liu Sen
Published: February 2024

Hibernation, a survival strategy in mammals for extreme climates, induces physiological phenomena such as ischemia–reperfusion and metabolic shifts that hold great potential for advancements in modern medicine. Despite this, the molecular mechanisms underpinning hibernation remain largely unclear. This study used RNA‐seq and Iso‐seq techniques to investigate the changes in liver transcriptome expression of Rhinolophus pusillus during hibernation and active periods, as well as under different microhabitat temperatures. We identified 11 457 differentially expressed genes during hibernation and active periods, of which 395 showed significant differential expression. Genes associated with fatty acid catabolism were significantly upregulated during hibernation, whereas genes related to carbohydrate metabolism and glycogen synthesis were downregulated. Conversely, immune‐related genes displayed differential expression patterns: genes tied to innate immunity were significantly upregulated, while those linked to adaptive immunity and inflammatory response were downregulated. The analysis of transcriptomic data obtained from different microhabitat temperatures revealed that R. pusillus exhibited an upregulation of genes associated with lipid metabolism in lower microhabitat temperature. This upregulation facilitated an enhanced utilization rate of triglyceride, ultimately resulting in increased energy provision for the organism. Additionally, R. pusillus upregulated gluconeogenesis‐related genes regardless of the microhabitat temperature, demonstrating the importance of maintaining blood glucose levels during hibernation. Our transcriptomic data reveal that these changes in liver gene expression optimize energy allocation during hibernation, suggesting that liver tissue adaptively responds to the inherent stress of its function during hibernation. This study sheds light on the role of differential gene expression in promoting more efficient energy allocation during hibernation. It contributes to our understanding of how liver tissue adapts to the stressors associated with this state.
Patellar Lateralization, Absence of Joint Hypermobility, and the Mechanism of Injury Are Associated With Osteochondral Fracture After First-time Acute Lateral Patellar Dislocation in Adolescents: An MRI-based Evaluation
Authors: İğrek Servet , Şahbat Yavuz , Koç Erdem , Çeliksöz Aytek Hüseyin , Topkar Osman Mert
Published: February 2024

Background:

Although the risk factors for patellofemoral dislocation are clearly defined, risk factors for osteochondral fracture (OCF) after patellar dislocation are not as well defined. The aim of this study was to investigate the risk factors for OCF by evaluating patients with and without OCF after first-time acute patellar dislocation.

Methods:

This multicenter study was conducted as a retrospective examination of the radiologic measurements on the magnetic resonance imaging of 306 patients. The patients were divided into the OCF group and non-OCF group, and OCFs were grouped according to whether the fracture was in the patella or femur. Patellar height, patellar lateralization, trochlear morphology, patellofemoral matching, and patella types were evaluated on patient magnetic resonance imaging. The presence of joint hypermobility in the patients was determined according to the Beighton scale score. The injury mechanisms of the patients were grouped as sports-related injuries, injuries resulting from simple falls, and injuries during daily activities.

Results:

A total of 120 OCFs were detected in 108 (35.2%) patients, of which 96 (80%) were in the patella and 24 (20%) in the femur. The rate of OCF after sports-related injuries was found to be significantly higher than in other injury mechanisms (P=0.001). More joint hypermobility was detected in patients without OCF (P=0.041). The measurements of tibial tubercle–trochlear groove, tibial tubercle–posterior cruciate ligament distance and lateral patellar displacement were statistically higher in cases with OCF (P=0.001). In patients with normal joint mobility, the rate of OCF localization in the patella was significantly higher (P=0.035). No correlation was found between any other parameters and OCF (P>0.05). The absence of joint hypermobility and the measurements of tibial tubercle–trochlear groove distance, tibial tubercle–posterior cruciate ligament distance, and lateral patellar displacement were independent risk factors for the incidence of OCF according to the logistic regression analysis.

Conclusions:

The absence of joint hypermobility and patellar lateralization are independent risk factors for the occurrence of OCF after first-time patellar dislocation. Sports-related injury is a nonindependent risk factor for the presence of OCF. In patients with normal joint mobility, the incidence of OCF in the patella is higher than in the femur. These important factors should be considered when evaluating patients and starting their treatment.

Level of Evidence:

Level III—retrospective cohort study.
Recent advances and remaining challenges in lung cancer therapy
Authors: Barr Tasha , Ma Shoubao , Li Zhixin , Yu Jianhua
Published: February 2024

Lung cancer remains the most common cause of cancer death. Given the continued research into new drugs and combination therapies, outcomes in lung cancer have been improved, and clinical benefits have been expanded to a broader patient population. However, the overall cure and survival rates for lung cancer patients remain low, especially in metastatic cases. Among the available lung cancer treatment options, such as surgery, radiation therapy, chemotherapy, targeted therapies, and alternative therapies, immunotherapy has shown to be the most promising. The exponential progress in immuno-oncology research and recent advancements made in the field of immunotherapy will further increase the survival and quality of life for lung cancer patients. Substantial progress has been made in targeted therapies using tyrosine kinase inhibitors and monoclonal antibody immune checkpoint inhibitors with many US Food And Drug Administration (FDA)-approved drugs targeting the programmed cell death ligand-1 protein (e.g., durvalumab, atezolizumab), the programmed cell death-1 receptor (e.g., nivolumab, pembrolizumab), and cytotoxic T-lymphocyte-associated antigen 4 (e.g., tremelimumab, ipilimumab). Cytokines, cancer vaccines, adoptive T cell therapies, and Natural killer cell mono- and combinational therapies are rapidly being studied, yet to date, there are currently none that are FDA-approved for the treatment of lung cancer. In this review, we discuss the current lung cancer therapies with an emphasis on immunotherapy, including the challenges for future research and clinical applications.
Postcardiac Injury Syndrome After Cardiac Surgery: An Evidence-Based Review
Authors: Tahir Muhammad Hamza , Sohail Sidra , Shahid Daniyal , Hussain Iqbal , Malik Jahanzeb , Iqra Syeda , Faraz Maria
Published: February 2024

Postcardiac injury syndrome (PCIS) serves as a comprehensive term encompassing a spectrum of conditions, namely postpericardiotomy syndrome, postmyocardial infarction (MI) related pericarditis (Dressler syndrome), and post-traumatic pericarditis stemming from procedures like percutaneous coronary intervention or cardiac implantable electronic device placement. These conditions collectively give rise to PCIS, triggered by cardiac injury affecting pericardial or pleural mesothelial cells, leading to subsequent inflammation syndromes spanning from uncomplicated pericarditis to substantial pleural effusion. A thorough literature search conducted on MEDLINE/PubMed utilizing search terms including “postacute cardiac injury syndrome,” “postcardiac injury syndrome,” “postcardiotomy syndrome,” “postpericardiotomy syndrome,” and “post-MI pericarditis” was instrumental in collating pertinent studies. To encapsulate the amassed evidence, relevant full-text materials were meticulously selected and amalgamated narratively. The pathophysiology of PCIS is proposed to manifest through an autoimmune-mediated process, particularly in predisposed individuals. This process involves the development of anti-actin and antimyosin antibodies after a cascade of cardiac injuries in diverse forms. Treatment strategies aimed at preventing recurrent PCIS episodes have shown efficacy, with colchicine and nonsteroidal anti-inflammatory drugs, including ibuprofen, demonstrating positive outcomes. Conversely, corticosteroids have exhibited no discernible benefit concerning prognosis or recurrence rates for this ailment. In summary, PCIS serves as a unifying term encompassing a spectrum of cardiac injury-related syndromes. A comprehensive review of relevant literature underscores the autoimmune-mediated pathophysiology in susceptible individuals. The therapeutic landscape involves the proficient use of colchicine and Nonsteroidal anti-inflammatory drugs to deter recurrent PCIS episodes, while corticosteroids do not appear to contribute to improved prognosis or reduced recurrence rates. This nuanced understanding contributes to an enhanced comprehension of PCIS and its multifaceted clinical manifestations, potentially refining its diagnosis and management.
Changes in Psychotropic Drug Concentrations Across the Menstrual Cycle: A Pilot Study
Authors: Spadi Julia , Scherf-Clavel Maike , Leutritz Anna Linda , Hütz Barbara , Matentzoglu Maria , Nieberler Matthias , Kurlbaum Max , Hahner Stefanie , Bartmann Catharina , McNeill Rhiannon V. , Kittel-Schneider Sarah
Published: February 2024

Background:

The escalating prescription of psychopharmacological medications to women of reproductive age underscores the growing significance of sex-specific variations in pharmacotherapy. Despite this, clinical trials have largely overlooked these differences. Preliminary data indicate sex-specific variations in the neurobiology of affective disorders and in the metabolism, pharmacodynamics, and kinetics of therapeutic drugs. This underscores the imperative for a more nuanced exploration of menstrual cycle–dependent fluctuations in psychotropic drugs. This pilot study aimed to investigate drug and hormone fluctuations in female patients with affective disorders, aiming to enhance comprehension of the interplay between cycle-related hormone fluctuations and pharmacokinetics. The ultimate goal is to facilitate more effective and safer pharmacological therapy in the future.

Methods:

Blood samples were collected from 27 patients and 27 age-matched control participants at 3 distinct time points (early follicular phase, ovulation, and late luteal phase) during each menstrual cycle. Depressive and manic symptoms were assessed, and hormone concentrations were measured in the entire sample, while drug concentrations were assessed solely in the affective disorder sample using mass spectrometry.

Results:

Significant variations in drug concentration were observed throughout the menstrual cycle for bupropion, with a trend toward altered concentration for venlafaxine. Moreover, notable differences in hormone concentrations were identified between patients and controls, even after accounting for the impact of contraceptive use, diagnoses, and medication.

Conclusions:

This pilot study reinforces previously reported data, underscoring the significance of sex-specific pharmacological therapy approaches. It provides further evidence supporting the interaction among sex hormones, drugs, and symptoms of affective disorders.
PRETREATED LHAM GRAFT COVERING FOR RETINAL DETACHMENT WITH POSTERIOR RETINAL BREAKS ABOVE CHORIORETINAL ATROPHY IN PATHOLOGIC MYOPIA
Authors: Lin Wei , Chen Hao , Tang Yongping , Lin Xiaoyan , Wei Yong
Published: February 2024

Purpose

To compare the surgical results of vitrectomy with untreated or pretreated lyophilized human amniotic membrane (LhAM) grafts covering in treating retinal detachment (RD) related to posterior retinal breaks above chorioretinal atrophy (CRA) in pathologic myopia (PM).

Methods

Nineteen patients with RD related to macular hole (MH) located above macular atrophy (MA) and/or posterior paravascular retinal breaks (PRBs) located above patchy CRA in PM were included. These eyes underwent vitrectomy with untreated LhAM covering (n = 10) or perfluorocarbon liquid (PFCL)-assisted pretreated LhAM covering (n = 9; grafts were pretreated in 0.125% indocyanine green and 50% hypertonic glucose solution for 15 to 20 minutes). The closure of the MH or PRBs, reattachment of the retina and best corrected visual acuity (BCVA) were measured postoperatively.

Results

Postoperatively, graft dislocation or shift was only found in 2 eyes (20%) in the untreated group. The closure rate of the MH or PRBs was 80% (8/10) and 100% (9/9) in the untreated group and pretreated group, respectively. The occurrence rate of excessive gliosis was 40% and 11% in the untreated group and the pretreated group, respectively. In both groups. BCVA was improved and the retinal reattachment rate was 100% at the final visit.

Conclusions

PFCL-assisted pretreated LhAM graft covering was effective in treating RD related to MH and/or PRBs situated above MA or patchy CRA in PM. This technique appeared to reduce graft dislocation or shift, promote the closures of MHs/PRBs, and reduce the occurrence of gliosis.
The Making of a Health Profession: How Chinese Medicine Became a Nationally Registered Allied Health Profession in Australia
Authors: McDonald John L , James Judy B
Published: February 2024

In 2012, traditional Chinese medicine (TCM) practitioners in Australia became nationally-registered allied health professionals in three categories: acupuncturist, Chinese herbal medicine practitioner, and Chinese herbal medicine dispenser. Australia was the first Western country to introduce national registration for Chinese medicine, followed by Portugal and, recently, New Zealand. The practice of TCM in Australia can be traced back to the beginning of Chinese immigration to Australia during the Victorian Gold Rush which began in the 1850s. The process which led to national registration commenced in the early 1970s with the establishment of the first acupuncture courses.

Decades of gradual development of courses from unaccredited part-time diplomas to accredited bachelor degrees, and the development, by the profession, of national consensus on educational standards were essential elements in the process which led to registration. Professional associations, such as the Australian Acupuncture and Chinese Medicine Association Ltd (AACMA), also developed a framework of professional self-regulation, including Codes of Ethics, Codes of Conduct, ongoing professional development requirements and Infection Control Guidelines, and provided leadership in the development of the profession.

After decades of tribalism and division within the TCM profession, the National Academic Standards Committee brought almost all stakeholders together to reach a consensus on the Australian Guidelines for Traditional Chinese Medicine Education which were published by AACMA in 2001. Professional associations also collaborated on joint submissions to the government in support of registration, which was introduced first in the state of Victoria in 2000, and subsequently became national in 2012.

Despite national registration, some barriers still remain, and professional associations continue to lobby the federal government for inclusion in Medicare, chronic disease management scheme, and Veterans Affairs.
The Transmission, Establishment and Cross-Cultural Integration of Chinese Medicine in the Mainstream Healthcare, through the Eyes of a Generation of Visionaries and Pioneers
Authors: Solos Ioannis , Buck Charles
Published: February 2024

It has historically been very difficult to trace the history of the westward transmission of Chinese Medicine through the accounts of its protagonists. Many of the early scholars such as Jack Worsley, Dick Van Buren, and Jo Goodman were reluctant to divulge information about the source of their knowledge, or their professional qualifications. Others, such as John Shen and Hong Yuan-bain were early 20th century immigrants who transmitted highly personalized versions of acupuncture and Chinese medicine to select disciples. Eventually, a new class of scholars appeared, including names such as Ted Kaptchuk, Peter Deadman, Nigel Wiseman, Will Morris, Peter Eckman, John McDonald, Charles Buck, and the late Giovanni Maciocia who looked for answers back in China, developed translation methodologies and terminology, compiled the main textbooks currently in use at TCM Colleges, overcame enormous scholastic adversity, developed courses and pursued the regulation and accreditation of TCM in various countries. This special issue synopsizes the path towards the global acculturation of TCM over the last 50 years, the main protagonists, the enormous accomplishments they have achieved for the profession, their philosophy, their clinical perspectives and vision for the future.
Surgical resection for hepatocellular carcinoma: a single-centre’s one decade of experience
Authors: Syaiful Ridho Ardhi , Mazni Yarman , Siagian Natan Kevin Partogu , Putranto Agi Satria , Jeo Wifanto Saditya , Rahadiani Nur , Ibrahim Febiansyah , Sihardo Lam , Marbun Vania Myralda Giamour , Lalisang Arnetta Naomi Louise , Lalisang Toar Jean Maurice
Published: February 2024

Background and aims:

Liver cancer is the third leading cause of global cancer deaths, and hepatocellular carcinoma is its most common type. Liver resection is one of the treatment options for hepatocellular carcinoma (HCC). This study aims to explore our hospital’s more than a decade of experience in liver resection for HCC patients.

Methods:

This is a retrospective cohort study on HCC patients undergoing resection from 2010 to 2021 in a tertiary-level hospital in Jakarta, Indonesia. Mortality rates were explored as the primary outcome of this study. Statistical analysis was done on possible predictive factors using Pearson’s χ2. Survival analysis was done using the Log-Rank test and Cox Regression.

Results:

Ninety-one patients were included in this study. The authors found that the postoperative mortality rates were 8.8% (in hospital), 11.5% (30 days), and 24.1% (90 days). Excluding postoperative mortalities, the long-term mortality rates were 44.4% (first year), 58.7% (3 years), and 69.7% (5 years). Cumulatively, the mortality rates were 46.4% (1 year), 68.9% (3 years), 77.8% (5 years), and 67.0% (all time). Significant predictive factors for cumulative 1-year mortality include large tumour diameter [odds ratio (OR) 14.06; 95% CI: 2.59–76.35; comparing <3 cm and >10 cm tumours; P<0.01], positive resection margin (OR 2.86; 1.17–77.0; P=0.02), and tumour differentiation (P=0.01). Multivariate analysis found hazard ratios of 6.35 (2.13–18.93; P<0.01) and 1.81 (1.04–3.14; P=0.04) for tumour diameter and resection margin, respectively.

Conclusion:

The mortality rate of HCC patients undergoing resection is still very high. Significant predictive factors for mortality found in this study benefit from earlier diagnosis and treatment; thus, highlighting the importance of HCC surveillance programs.
The role of hydrogels in the management of brain tumours: a narrative review
Authors: Anas Zahra , Hasan Syeda Fatima Saba , Moiz Muhammad Abdul , Zuberi Muhammad Abdul Wasay , Shah Hussain Haider , Ejaz Aima , Dave Tirth , Panjwani Muhammad Hasnain , Rauf Sameer Abdul , Hussain Muhammad Sheheryar , Waseem Radeyah
Published: February 2024

Conventional therapeutic techniques for brain tumours have limitations and side effects, necessitating the need for alternative treatment options. MRI-monitored therapeutic hydrogel systems show potential as a non-surgical approach for brain tumour treatment. Hydrogels have unique physical and chemical properties that make them promising for brain tumour treatment, including the ability to encapsulate therapeutic agents, provide sustained and controlled drug release, and overcome the blood-brain barrier for better penetration. By combining hydrogel systems with MRI techniques, it is possible to develop therapeutic approaches that provide real-time monitoring and controlled release of therapeutic agents. Surgical resection remains important, but there is a growing need for alternative approaches that can complement or replace traditional methods. The objective of this comprehensive narrative review is to evaluate the potential of MRI-monitored therapeutic hydrogel systems in non-surgical brain tumour treatment
Gut microbiota and greenness co-exposure contributed to maternal prenatal depression
Authors: Fang Qingbo , Qiu Tianlai , Liu Yanqun
Published: February 2024

Objectives:

Previous studies have reported an association between depression with gut microbiota and residential greenness exposure. The aim of our study was to explore whether gut microbiota and residential greenness co-exposure contributed to maternal prenatal depression.

Methods:

We collected demographic information, stool samples, and exposure to residential greenness from 75 pregnant women in the third trimester. Participants were divided into prenatal depression group and control group according to the score of Edinburgh Postnatal Depression Scale (EPDS). Gut microbiota was analyzed using 16S rRNA V3/V4 gene sequence. Residential greenness [normalized difference vegetation index (NDVI)] during pregnancy was calculated using database of National Science and Technology Infrastructure of China.

Results:

There were significant differences between gut microbial composition in two groups. Phylum Patescibacteria (OR=5.34*e4, 95% CI: 1.48 - 1.92*e9, P-value=0.042) and greenness exposure (OR=0.15, 95% CI: 0.04 - 0.63, P-value=0.010) significantly contributed to prenatal depression, which indicated the protective effects of greenness exposure to prenatal depression. And Adlercreutzia (OR=1.44*e4, 95% CI: 2.70 – 7.70*e9, P-value=0.032) and greenness exposure (OR=0.39, 95% CI: 0.21 – 0.73, P-value=0.003) also significantly contributed to prenatal depression.

Conclusions:

Our study highlights that gut microbiota and greenness co-exposure during pregnancy contributed to maternal prenatal depression. Further research is needed to explore the mechanisms contributing to the co-exposure of gut microbiota and greenness associated with depression in pregnant women.
Predictive models based on machine learning for early recurrence and metastasis in postoperative patients with colorectal cancer
Authors: Dong Qian , Mo Minghui , Huang Xia , Sun Xia , Jia Peipei , Wang Ting , Liu Cuiping
Published: February 2024

Objectives:

To construct and validate a prediction model based on machine learning algorithms for early recurrence and metastasis in patients with colorectal cancer after surgery.

Methods:

This study employed a prospective cohort design. A total of 498 postoperative patients with colorectal cancer, treated at an affiliated hospital of Qingdao University, were recruited using convenience sampling from June to December 2021. Data were collected during outpatient visits and hospitalizations. The risk factors for early recurrence and metastasis of colorectal cancer were determined through multivariate logistic regression analysis in SPSS 26.0 software. Using Python 3.7.0 software, four machine learning algorithms (logistic regression, Support Vector Machine, XGBoost, and LightGBM) were used to develop and validate prediction models for early recurrence and metastasis of colorectal cancer after surgery.

Results:

Of the 498 patients, 51 (10.24%) had early recurrence and metastasis. Multivariate logistic regression analysis showed that personal traits (family history of cancer, histological type, degree of tumor differentiation, number of positive lymph nodes, and T stage), behaviour and/or lifestyle (intake of refined grains, whole grains, fish, shrimp, crab, and nuts, as well as resilience), and interpersonal networks (social support) were all associated with early recurrence and metastasis of colorectal cancer (P<0.05). The logistic regression prediction model showed the best prediction performance out of the four models, with an accuracy rate of 0.920, specificity of 0.982, F1 of 0.495, AUC of 0.867, Kappa of 0.056, and Brier score of 0.067.

Conclusion:

Our findings suggest that a prediction model based on logistic regression could accurately and scientifically predict which patients are likely to experience early recurrence and metastasis, helping to lessen the burden for both patients and the healthcare system.
Using Data-To-Care Strategies to Optimize the HIV Care Continuum in Connecticut: Results From a Randomized Controlled Trial
Authors: Machavariani Eteri , Miceli Janet , Altice Frederick L. , Fanfair Robyn Neblett , Speers Suzanne , Nichols Lisa , Jenkins Heidi , Villanueva Merceditas
Published: February 2024

Background:

Re-engaging people with HIV who are newly out-of-care remains challenging. Data-to-care (D2C) is a potential strategy to re-engage such individuals.

Methods:

A prospective randomized controlled trial compared a D2C strategy using a disease intervention specialist (DIS) vs standard of care where 23 HIV clinics in 3 counties in Connecticut could re-engage clients using existing methods. Using a data reconciliation process to confirm being newly out-of-care, 655 participants were randomized to DIS (N = 333) or standard of care (N = 322). HIV care continuum outcomes included re-engagement at 90 days, retention in care, and viral suppression by 12 months. Multivariable regression models were used to assess factors predictive of attaining HIV care continuum outcomes.

Results:

Participants randomized to DIS were more likely to be re-engaged at 90 days (adjusted odds ratios [aOR] = 1.42, P = 0.045). Independent predictors of re-engagement at 90 days were age older than 40 years (aOR = 1.84, P = 0.012) and perinatal HIV risk category (aOR = 3.19, P = 0.030). Predictors of retention at 12 months included re-engagement at 90 days (aOR = 10.31, P < 0.001), drug injection HIV risk category (aOR = 1.83, P = 0.032), detectable HIV-1 RNA before randomization (aOR = 0.40, P = 0.003), and county (Hartford aOR = 1.74, P = 0.049; New Haven aOR = 1.80, P = 0.030). Predictors of viral suppression included re-engagement at 90 days (aOR = 2.85, P < 0.001), retention in HIV care (aOR = 7.07, P < 0.001), and detectable HIV-1 RNA prerandomization (aOR = 0.23, P < 0.001).

Conclusions:

A D2C strategy significantly improved re-engagement at 90 days. Early re-engagement improved downstream benefits along the HIV care continuum like retention in care and viral suppression at 12 months. Moreover, other factors predictive of care continuum outcomes can be used to improve D2C strategies.
Brief Report: Differentiated Service Delivery Framework for People With Multidrug-Resistant Tuberculosis and HIV Coinfection
Authors: Reis Karl , Wolf Allison , Perumal Rubeshan , Seepamore Boitumelo , Guzman Kevin , Ross Jesse , Cheung Ying Kuen K. , Amico K. Rivet , Brust James C. M. , Padayatchi Nesri , Friedland Gerald , Naidoo Kogieleum , Daftary Amrita , Zelnick Jennifer , O'Donnell Max
Published: February 2024

Introduction:

For people living with HIV/AIDS, care is commonly delivered through differentiated service delivery (DSD). Although people with multidrug-resistant tuberculosis (MDR-TB) and HIV/AIDS experience severe treatment-associated challenges, there is no DSD model to support their treatment. In this study, we defined patterns of medication adherence and characterized longitudinal barriers to inform development of an MDR-TB/HIV DSD framework.

Methods:

Adults with MDR-TB and HIV initiating bedaquiline (BDQ) and receiving antiretroviral therapy (ART) in KwaZulu-Natal, South Africa, were enrolled and followed through the end of MDR-TB treatment. Electronic dose monitoring devices measured BDQ and ART adherence. Longitudinal focus groups were conducted and transcripts analyzed thematically to describe discrete treatment stage-specific and cross-cutting treatment challenges.

Results:

Two hundred eighty-three participants were enrolled and followed through treatment completion (median 17.8 months [interquartile range 16.5–20.2]). Thirteen focus groups were conducted. Most participants (82.7%, 234/283) maintained high adherence (mean BDQ adherence 95.3%; mean ART adherence 85.5%), but an adherence-challenged subpopulation with <85% cumulative adherence (17.3%, 49/283) had significant declines in mean weekly BDQ adherence from 94.9% to 39.9% (P < 0.0001) and mean weekly ART adherence from 83.9% to 26.6% (P < 0.0001) over 6 months. Psychosocial, behavioral, and structural obstacles identified in qualitative data were associated with adherence deficits in discrete treatment stages and identified potential stage-specific interventions.

Conclusions:

A DSD framework for MDR-TB/HIV should intensify support for adherence-challenged subpopulations, provide multimodal support for adherence across the treatment course, and account for psychosocial, behavioral, and structural challenges linked to discrete treatment stages.
PRMT6-FOXO3A ATTENUATES APOPTOSIS BY UPREGULATING PARKIN EXPRESSION IN INTESTINAL ISCHEMIA-REPERFUSION INJURY
Authors: Wu Xinwan , Zhou Yu , Xu Hongjiao , Zhang Xinyi , Yao Liangfang , Li Jinbao , Li Xiang
Published: February 2024

Intestinal ischemia-reperfusion injury (IIRI) is a serious disease with high morbidity and mortality. This study aims to investigate the potential regulatory mechanisms involving protein arginine methyltransferase 6 (PRMT6), Forkhead box O3a (FoxO3a), and Parkin in IIRI and elucidate their roles in mediating cell apoptosis. The IIRI animal model was established and confirmed using hematoxylin and eosin staining. Oxygen-glucose deprivation and reperfusion (OGD/R) cell model was established to mimic ischemic injury in vitro. Transient transfection was used to overexpress or knock down genes. Cell death or apoptosis was assessed by propidium iodide staining, terminal deoxynucleotidyl transferase dUTP nick end labeling assay, and flow cytometry. The expression of proteins was detected by western blot. The histopathology observed by hematoxylin and eosin staining suggested that the IIRI animal model was successfully established. Our findings revealed that IIRI resulted in increased Bax and decreased Bcl-2 levels. In vitro experiments showed that overexpression of Parkin decreased OGD/R injury and suppressed elevation of Bax/Bcl-2. PRMT6 regulated the methylation level of FoxO3a. Moreover, FoxO3a directly binds to Parkin, and FoxO3a overexpression reduced OGD/R-induced cell death and regulation of Parkin. Overexpression of PRMT6 can attenuate the downregulation of Parkin and elevation of Bax/Bcl-2 caused by OGD/R. Knockdown of PRMT6 promoted apoptosis in intestinal epithelial cells of OGD/R group, while PRMT6 overexpression exhibited the opposite effect. Notably, the levels of PRMT6, FoxO3a, and Parkin were decreased in IIRI mouse intestinal tissue. Knocking out PRMT6 causes a significant decrease in the lifespan of mice. Altogether, our results demonstrated that PRMT6 upregulated the expression of Parkin by regulating FoxO3a methylation level, attenuating the apoptosis induced by IIRI.
Recent Changes in the Management of High-Grade Blunt Pancreatic Injury in Children: A Nationwide Trend Analysis
Authors: Katsura Morihiro , Ikenoue Tatsuyoshi , Aoki Makoto , Kuriyama Akira , Takahashi Kyosuke , Schellenberg Morgan , Martin Matthew J , Inaba Kenji , Matsushima Kazuhide
Published: February 2024

BACKGROUND:

The optimal management of pediatric patients with high-grade blunt pancreatic injury (BPI) involving the main pancreatic duct remains controversial. This study aimed to assess the nationwide trends in the management of pediatric high-grade BPI at pediatric (PTC), mixed (MTC), and adult trauma centers (ATC).

STUDY DESIGN:

This is a retrospective observational study of the National Trauma Data Bank. We included pediatric patients (age 16 years or less) sustaining high-grade BPI (Abbreviated Injury Scale 3 or more) from 2011 to 2021. Patients who did not undergo pancreatic operation were categorized into the nonoperative management (NOM) group. Trauma centers were defined as PTC (level I/II pediatric only), MTC (level I/II adult and pediatric), and ATC (level I/II adult only). Primary outcome was the proportion of patients undergoing NOM, and secondary outcomes included the use of ERCP and in-hospital mortality. A Cochran–Armitage test was used to analyze the trend.

RESULTS:

A total of 811 patients were analyzed. The median age was 9 years (interquartile range 6 to 13), 64% were male patients, and the median injury severity score was 17 (interquartile range 10 to 25). During the study period, there was a significant upward linear trend in the use of NOM and ERCP among the overall cohort (range 48% to 66%; ptrend = 0.033, range 6.1% to 19%; ptrend = 0.030, respectively). The significant upward trend for NOM was maintained in the subgroup of patients at PTC and MTC (ptrend = 0.037), whereas no significant trend was observed at ATC (ptrend = 0.61). There was no significant trend in in-hospital mortality (ptrend = 0.38).

CONCLUSIONS:

For the management of pediatric patients with high-grade BPI, this study found a significant trend toward increasing use of NOM and ERCP without mortality deterioration, especially at PTC and MTC.
It's more than the amount that counts: implications of collagen organization on passive muscle tissue properties revealed with micromechanical models and experiments
Authors: Sahani Ridhi , Hixson Kaitlyn , Blemker Silvia S.
Published: February 2024

Collagen accumulation is often used to characterize skeletal muscle fibrosis, but the role of collagen in passive muscle mechanics remains debated. Here we combined finite-element models and experiments to examine how collagen organization contributes to macroscopic muscle tissue properties. Tissue microstructure and mechanical properties were measured from
in vitro
biaxial experiments and imaging in dystrophin knockout (
mdx
) and wild-type (WT) diaphragm muscle. Micromechanical models of intramuscular and epimuscular extracellular matrix (ECM) regions were developed to account for complex microstructure and predict bulk properties, and directly calibrated and validated with the experiments. The models predicted that intramuscular collagen fibres align primarily in the cross-muscle fibre direction, with greater cross-muscle fibre alignment in
mdx
models compared with WT. Higher cross-muscle fibre stiffness was predicted in
mdx
models compared with WT models and differences between ECM and muscle properties were seen during cross-muscle fibre loading. Analysis of the models revealed that variation in collagen fibre distribution had a much more substantial impact on tissue stiffness than ECM area fraction. Taken together, we conclude that collagen organization explains anisotropic tissue properties observed in the diaphragm muscle and provides an explanation for the lack of correlation between collagen amount and tissue stiffness across experimental studies.
Assessment of the nano-mechanical properties of healthy and atherosclerotic coronary arteries by atomic force microscopy
Authors: Savvopoulos Fotios , Keeling Michael C. , Carassiti Daniele , Fogell Nicholas A. , Patel Miten B. , Naser Jarka , Gavara Núria , de Silva Ranil , Krams Rob
Published: February 2024

Nano-indentation techniques might be better equipped to assess the heterogeneous material properties of plaques than macroscopic methods but there are no bespoke protocols for this kind of material testing for coronary arteries. Therefore, we developed a measurement protocol to extract mechanical properties from healthy and atherosclerotic coronary artery tissue sections. Young's modulus was derived from force-indentation data. Metrics of collagen fibre density were extracted from the same tissue, and the local material properties were co-registered to the local collagen microstructure with a robust framework. The locations of the indentation were retrospectively classified by histological category (healthy, plaque, lipid-rich, fibrous cap) according to Picrosirius Red stain and adjacent Hematoxylin & Eosin and Oil-Red-O stains. Plaque tissue was softer (
p
< 0.001) than the healthy coronary wall. Areas rich in collagen within the plaque (fibrous cap) were significantly (
p
< 0.001) stiffer than areas poor in collagen/lipid-rich, but less than half as stiff as the healthy coronary media. Young's moduli correlated (Pearson's
ρ
= 0.53,
p
< 0.05) with collagen content. Atomic force microscopy (AFM) is capable of detecting tissue stiffness changes related to collagen density in healthy and diseased cardiovascular tissue. Mechanical characterization of atherosclerotic plaques with nano-indentation techniques could refine constitutive models for computational modelling.
Is SARS-CoV-2 elimination or mitigation best? Regional and disease characteristics determine the recommended strategy
Authors: Martignoni Maria M. , Arino Julien , Hurford Amy
Published: February 2024

Public health responses to the COVID-19 pandemic varied across the world. Some countries (e.g., mainland China, New Zealand, and Taiwan) implemented elimination strategies involving strict travel measures and periods of rigorous nonpharmaceutical interventions (NPIs) in the community, aiming to achieve periods with no disease spread; while others (e.g., many European countries and the United States of America) implemented mitigation strategies involving less strict NPIs for prolonged periods, aiming to limit community spread. Travel measures and community NPIs have high economic and social costs, and there is a need for guidelines that evaluate the appropriateness of an elimination or mitigation strategy in regional contexts. To guide decisions, we identify key criteria and provide indicators and visualizations to help answer each question. Considerations include determining whether disease elimination is: (1) necessary to ensure health care provision; (2) feasible from an epidemiological point of view; and (3) cost effective when considering, in particular, the economic costs of travel measures and treating infections. We discuss our recommendations by considering the regional and economic variability of Canadian provinces and territories, and the epidemiological characteristics of different SARS-CoV-2 variants. While elimination may be a preferable strategy for regions with limited health care capacity, low travel volumes, and few port of entries, mitigation may be more feasible in large urban areas with dense infrastructure, strong economies, and with high connectivity to other regions.
GenerRNA: A generative pre-trained language model forde novoRNA design
Authors: Zhao Yichong , Oono Kenta , Takizawa Hiroki , Kotera Masaaki
Published: February 2024

Abstract

The design of RNA plays a crucial role in developing RNA vaccines, nucleic acid therapeutics, and innovative biotechnological tools. Nevertheless, existing techniques lack versatility across various tasks and frequently suffer from a deficiency of automated generation. Inspired by the remarkable success of Large Language Models (LLMs) in the realm of protein and molecule design, we present GenerRNA, the first large-scale pre-trained model for RNA generation, aiming to further automate RNA design. Our approach eliminates the need for secondary structure or other prior knowledge and is capable ofde novogeneration of RNA with stable secondary structures while ensuring its distinctiveness from existing sequences. This widens our exploration of RNA space, thereby enriching our understanding of RNA structures and functions. Moreover, GenerRNA is fine-tunable on smaller, more specialized datasets for particular subtasks. This flexibility and versatility enables the generation of RNAs with desired specific functionalities or properties. Upon fine-tuning GenerRNA, we successfully generated novel RNA sequences exhibiting high affinity for target proteins. GenerRNA is freely available at the following repository:https://github.com/pfnet-research/GenerRNA
Don’t Leave the Past Behind: How Larval Experience Shapes Pupal Antipredator Response inAedes aegypti
Authors: Rawat Kanika , Bhambore Akshaye Anand , Isvaran Kavita
Published: February 2024

Animals use predation encounters or risk experiences to influence their future antipredator responses. Such carryover effects of predation can benefit them by enhancing their antipredator behaviour and thereby decreasing their risk of mortality through predation. Despite these fitness benefits, behavioural carryovers of predation past may not be a common phenomenon in complex life cycles. Complex life cycles pose a unique evolutionary and physiological challenge to behavioural carryovers since every life stage is distinct in morphology, physiology, and function. Each life stage of a complex life cycle is expected to evolve its independent response based on the real-time threat level and manage the trade-offs accordingly. Along with the evolutionary challenge, physiological barriers can hamper behavioural carryovers, especially in holometabolous insects, where we observe extensive tissue remodelling and developmental compartmentalisation. We investigated behavioural carryover in the holometabolous mosquito model system,Aedes aegypti. We asked whether predation risk during a life stage carries over to the subsequent stage, influencing its behaviour, or if the next life stage responds according to its threat environment.Aedes aegyptihas four major stages– egg, larva, pupa, and adult. We examined the effect of predation-risk experience across larval and pupal stages. Larval and pupal stages differ in morphology, physiology and function. They share the same habitat and, therefore, similar threats. We manipulated the threat of predation experienced by larvae and investigated its influence on pupal behaviour. We found behavioural carryover in the pupal stage for the first time and discovered exciting interactions between past experiences and the current threat environment. Our study underscores the crucial role of predation pressure in shaping the evolution of complex life cycles, emphasising the significance of early experiences with predators in influencing behavioural traits across distinct life stages.