bluuebunny/crossref_metadata_2025 huggingface dataset:
Web based research in sexual medicine: a position statement of the European Society for Sexual Medicine
Authors: Kirana Paraskevi-Sofia , Gudeloglu Ahmet , Sansone Andrea , Sokolakis Ioannis
Published: July 2023

Background

Although the use of the Web has brought major advances in every step of the research process, this also comes with several methodological challenges.

Aim

The article presents the European Society for Sexual Medicine's position statements on key methodological concerns relative to Web-based research in sexual medicine.

Methods

The authors conducted a systematic scoping review of articles using Web-based research methods in sexual medicine. For the creation of the statements, the authors processed the data from the methodology of the studies and formulated the final statements reaching 100% agreement in the group.

Outcomes

European Society for Sexual Medicine statements were provided on the following domains: definition of the population of interest, selection of the population of interest, data collection quality, response rate, self-reported questionnaire, consent, and legal obligations.

Results

Researchers should justify the relevance of the Internet population to the population of interest; should clearly describe how they identified study participants; should select and employ specific measures to avoid hoax; should explicitly describe the process of calculation of response and completion rates as well as the relative implications; should validate traditional sexual health questionnaires for online and, if possible, multilingual use; should not ignore consent in Web-based research; and need to be knowledgeable of the technical measures and legal obligations to protect anonymity.

Implications

Researchers are advised to include trained computer scientists in their group, have a good understanding of their legal obligations as to collecting, storing and disseminating personal data, and design their studies by taking into account the challenges of Web-based research.

Strengths and limitations

The heterogeneity of the included studies and methodological low quality of most of them was a limitation, which also shows the importance of this study and the need for guidelines regarding Web-based research.

Conclusion

Large uncontrolled samples could be a threat to the quality of the studies and increase bias if researchers are not mindful of the methodological challenges they would need to account for.
Tiny but Mighty: Nanoscale Materials in Plant Disease Management
Authors: Muthuramalingam Raja , Barroso Karol , Milagres Juliana , Tedardi Vitória , Franco de Oliveira Felipe , Takeshita Vanessa , Karmous Ines , El-Tanbouly Rania , da Silva Washington
Published: July 2023

Nanoscale materials are promising tools for managing plant diseases and are becoming important players in the current agritech revolution. However, adopting modern methodologies requires a broad understanding of their effectiveness in solving target problems and their effects on the environment and food chain. Furthermore, it is paramount that such technologies are mechanistically and economically feasible for growers to adopt in order to be sustainable in the long run. This Feature Article summarizes the latest findings on the role of nanoscale materials in managing agricultural plant pathogens. Herein, we discussed the benefits and limitations of using nanoscale materials in plant disease management and their potential impacts on the environment and global food security.
Treatment of COVID-19-Induced Systematic Inflammatory Response and Multiple Organ Failure Using Xuebijing
Authors: Chen Yao , Guo Jianbo , Peng Wei , Xiang Xiangyin , Wang Yifan , Luo Yi , Feng Yibin , Wong Vivian Taam , Chen Haiyong
Published: July 2023

According to clinical studies, patients with severe coronavirus disease 2019 (COVID-19) have a high incidence of cytokine storm and thrombosis. The National Health Commission of China approved Xuebijing (XBJ) as a first-line Chinese medicinal injection for COVID-19 patients with systemic inflammatory response syndrome (SIRS) and/or multiple organ failure (MOF). We hypothesized that the therapeutic effect of XBJ on SIRS and MOF in COVID-19 occurs via immunothrombosis and employed network pharmacology to evaluate this potential mechanism. The chemical compounds in XBJ were retrieved, and proteins related to thrombotic diseases were screened. Further, Gene Ontology enrichment analysis of the antithrombotic targets of XBJ was conducted. The results highlight the key inter-players (neutrophils, monocytes/macrophages, and platelets) of immunothrombosis in COVID-19 and the potential therapeutic mechanism of XBJ in suppressing oxidative stress, inflammation, apoptosis, and platelet aggregation. Severe COVID-19 patients with SIRS and MOF may benefit from XBJ as it exhibits anti-inflammatory effects, inhibits platelet activation, and induces lymphocyte apoptosis.
Using the community of inquiry as a framework to promote online teaching and learning in advanced practice nursing education
Authors: Padilla Blanca Iris
Published: July 2023

As advanced practice nursing education continues to shift toward a distance and hybrid format, it is important that nurse educators engaged in distance learning create and facilitate an online environment that successfully incorporates critical thinking, problem-solving skills, collaboration, and a sense of community. Although many learning theories and frameworks exist, there is a lack of literature on the applicability of these theories and frameworks to online teaching and learning in advanced practice nursing education. The purpose of this article is to describe the Community of Inquiry (CoI) framework and how it can be applied to online teaching and learning activities in advanced practiced nursing courses. This CoI is an effective framework for online learning and has been successful in promoting student engagement, an important factor in and predictor of academic success.
Understanding Poison: Study of a Word Du from the Perspective of Comparative History
Authors: LIU Yan
Published: July 2023

This article investigates the word Du (毒) in premodern Chinese medicine and culture. It highlights the paradoxical meaning of the word that served as a foundation for the therapeutic use of poisons in traditional Chinese medicine. The article then situates the study in a comparative framework. By comparing the Chinese notion of Du with the Greek concept of pharmakon, it demonstrates significant similarities on the medical use of poisons in the two cultures. It further identifies a striking difference: While the European pharmacy started to separate poisons from medicines in the medieval era, poisons remained an integral part of healing repertoire throughout imperial China. The article ends with offering some cultural explanations for this divergence, and more broadly, a distinct worldview as revealed by the intimate relationship between poisons and medicines in traditional Chinese pharmacy.
Pulmonary Langerhans cell histiocytosis – an update on pathogenesis and treatment
Authors: Jouenne Fanélie , Benattia Amira , Tazi Abdellatif
Published: July 2023

Purpose of review

Pulmonary Langerhans cell histiocytosis (PLCH) is a rare diffuse cystic lung disease that affects young to middle-aged smoking adults of both genders. The identification of molecular alterations in the canonical mitogen-activated protein kinase (MAPK) signalling pathway in most specific lesions has demonstrated the clonal/neoplastic nature of PLCH. We will summarize the progress made in the understanding of the pathogenesis of adult PLCH, and briefly highlight the recent findings useful for the management of the patients.

Recent findings

The MAPK pathway is constantly activated in PLCH lesions. Apart from the BRAF
V600E mutation, other driver somatic genomic alterations in this pathway (mainly MAP2K1 mutations/deletions and BRAF deletions) have been identified in the lesions, paving the way for targeted treatment. Smoking appears to promote the recruitment of MAPK-activated circulating myeloid precursors to the lung. The long-term survival of PLCH is more favourable with a 10-year survival >90%. Lung cancer and chronic respiratory failure are the main causes of death. Few patients develop severe pulmonary complications within the 5 years after diagnosis, justifying a close longitudinal follow-up of the patients.

PLCH is a MAPK driven neoplasia with inflammatory properties. The place of targeted therapies in severe forms of PLCH warrants further evaluation.
Prevalence and correlates of androgen dependence: a meta-analysis, meta-regression analysis and qualitative synthesis
Authors: Skauen Jenny Eriksrød , Pallesen Ståle , Bjørnebekk Astrid , Chegeni Razieh , Syvertsen André , Petróczi Andrea , Sagoe Dominic
Published: July 2023

Purpose of review

To investigate the prevalence and correlates of androgen dependence among users. A meta-analysis, meta-regression analysis, and qualitative synthesis were conducted based on a systematic literature search in Google Scholar, ISO Web of Science, PsycNET, and PubMed.

Recent findings

Twenty-six studies were included in the review and 18 studies (N = 1782) in the statistical analysis. The overall lifetime androgen dependence prevalence was 34.4% [95% confidence interval (CI): 27.8–41.7, Q = 113.1, I
2 = 85.0, P < 0.001]. Although males (36.1%, P < 0.001) and females (37.0%, P = 0.188) did not differ (Q = 0.0, P = 0.930) in dependence prevalence, controlling for other study characteristics, higher study male sample proportion was related to higher dependence prevalence. Combined interview and questionnaire assessments showed higher prevalence compared to interviews only. Publications from 1990–1999 generated higher prevalence compared to 2000–2009 and 2010–2023 publications. Dependents were associated with a wide array of demographic inequalities, and biophysical, cognitive, emotional, and psychosocial problems.

One of three persons who initiate androgen use experiences dependence along with various serious disorders. Androgen use and dependence should be considered an important public health issue requiring targeted health interventions.
Recent advances in anaplastic thyroid cancer management
Authors: Hamidi Sarah , Maniakas Anastasios
Published: July 2023

Purpose of review

To summarize recent developments in the diagnosis and management of patients with anaplastic thyroid cancer (ATC).

Recent findings

An updated edition of the Classification of Endocrine and Neuroendocrine Tumors was released by the World Health Organization (WHO), in which squamous cell carcinoma of the thyroid are now a subtype of ATC. Broader access to next generation sequencing has allowed better understanding of the molecular mechanisms driving ATC and improved prognostication. BRAF-targeted therapies revolutionized the treatment of advanced/metastatic BRAFV600E-mutated ATC, offering significant clinical benefit and allowing better locoregional control of disease through the neoadjuvant approach. However, inevitable development of resistance mechanisms represents a major challenge. Addition of immunotherapy to BRAF/MEK inhibition has shown very promising results and significant improvement in survival outcomes.

Major advancements took place in the characterization and management of ATC in recent years, especially in patients with a BRAF V600E mutation. Still, no curative treatment is available, and options are limited once resistance to currently available BRAF-targeted therapies develops. Additionally, there is still a need for more effective treatments for patients without a BRAF mutation.
Noninvasive brain stimulation for motor dysfunction after incomplete spinal cord injury: a systematic review and meta-analysis
Authors: Li Fang , Wei Changkun , Huo Su , Liu Xiuzhen , Du Jubao
Published: July 2023

Objective

We aimed to examine the effectiveness of noninvasive brain stimulation (NIBS) on motor dysfunction after incomplete spinal cord injury (iSCI).

Methods

The PubMed, Embase, and Cochrane Library were searched from the inception dates to April 30, 2022. Randomized controlled trials comparing the effects of NIBS and sham stimulation on motor dysfunction in patients with iSCI were included. Two reviewers performed the data extraction and assessed study quality using Cochrane Collaboration’s Tool. The primary outcomes involved upper limb function, lower limb function, spasticity, and activities of daily living. They were analyzed using meta-analysis method and the results were reported as SMD with 95% CI.

Results

14 studies involving 225 patients were included. NIBS reduced spasticity at the end of intervention (SMD = -0.68, 95% CI = -1.32 to -0.03, P = 0.04) and one-week follow-up (SMD = -0.82, 95% CI = -1.48 to -0.16, P = 0.02), but no beneficial effect at one-month follow-up (SMD = -0.32, 95% CI = -1.06 to 0.42, P = 0.39). Additionally, NIBS also increased lower limb muscle strength at one-month follow-up (SMD = 0.69, 95% CI = 0.11 to 1.28, P = 0.02). Other main outcomes were similar between groups.

Conclusion

NIBS can reduce spasticity, and the favorable effect can sustain for one week after intervention. Also, NIBS can increase lower limb muscle strength at one-month follow-up.
The Effect of Climate on the Dose Requirements of Botulinum Toxin A in Cosmetic Interventions
Authors: Borsky Kim L. , Rodrigues Jeremy N. , Rodrigues Raina
Published: July 2023

Background:

Botulinum toxin A to the glabella is a popular cosmetic intervention. Functional musculature differences may arise from chronic behavioral adjustment to high sun exposure levels, requiring greater doses. This could affect clinical practice globally. This study investigated the effect of climate on real-world doses.

Methods:

The authors conducted a comparative cohort study using data from a registry from a single provider practicing across two centers: the United Kingdom and Malta. They classified one center as low sun exposure (United Kingdom winter month treatment) and the other as high sun exposure (Malta summer months). Patients were followed up once every 3 weeks and received top-up doses until full clinical paralysis was achieved. To standardize the comparison, the study included only women aged 35 to 60 years undergoing glabellar botulinum toxin treatment by experienced clinicians following standard procedures from 2012 to 2019. Smokers, those not seeking maximal paralysis, those documented as not compliant with posttreatment advice, those with colds or fevers, and those with broken cold supply chains were excluded. Univariable and multivariable analyses were undertaken.

Results:

A total of 523 patients were included: 292 “high-sun” patients and 231 “low-sun” patients. Mean total doses were significantly higher in the high-sun group (29.2 units versus 27.3 units; P = 0.0031). When correcting for age in multivariable analysis, the low-sun group still had lower total dose requirements (P = 0.00574).

Conclusion:

Patients injected with glabellar botulinum toxin in high-sun climates may have significantly increased dose requirements to achieve maximal paralysis.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Therapeutic, III.
Prepectoral Two-Stage Implant-Based Breast Reconstruction with Poly-4-Hydroxybutyrate for Pocket Control without the Use of Acellular Dermal Matrix: A 4-Year Review
Authors: Movassaghi Kiya , Gilson Aaron , Stewart Christopher N. , Cusic Jenna , Movassaghi Aria
Published: July 2023

Background:

Absorbable mesh has been used to mitigate the potential drawbacks of acellular dermal matrix (ADM)–based breast reconstruction. Poly-4-hydroxybutyrate (P4HB) has been demonstrated to be a lower-cost, safe, and effective alternative to ADM in subpectoral breast reconstruction. In this study, the authors used P4HB for pocket control and implant support in immediate two-stage prepectoral breast reconstruction, examining nonintegration, capsular contracture, implant malposition, patient comorbidities, and risk factors.

Methods:

A retrospective review of a single surgeon’s (K.M.) experience was performed over a 4-year span for patients who had undergone immediate two-stage prepectoral implant-based breast reconstruction with P4HB mesh. Complications (implant loss, rippling, capsular contracture, and malposition) and patient satisfaction were examined.

Results:

From 2018 to 2022, 105 patients underwent breast reconstruction using P4HB mesh on a total of 194 breasts. P4HB mesh integration was 97%. Sixteen breasts (8.2%) experienced minor complications, and 10.3% of devices required explantation, which was significantly higher in the irradiated group at 28.6% (P < 0.01). Patients who were older, had a higher body mass index, were active smokers, or had an increased mastectomy specimen size were more likely to undergo explantation. The capsular contracture rate and overall lateral malposition rate were 1.0%. Visible rippling was present in 15.6% of breasts. There was no significant difference between smile mastopexy and inferolateral incision with regard to capsular contracture, lateral malposition, and rippling. Overall, patients demonstrated a high level of satisfaction. There were no significant predictors of capsular contracture, lateral malposition, or visible rippling.

Conclusions:

The authors show the safety and efficacy of P4HB in two-stage prepectoral breast reconstruction. There appears to be equal, if not reduced, capsular contracture rates when compared with the published data on ADM. This represents a large cost reduction to both the patient and the health care system.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Therapeutic, IV.
Smartphone Photoplethysmography Pulse Rate Covaries With Stress and Anxiety During a Digital Acute Social Stressor
Authors: Nelson Benjamin W. , Harvie Helen M. K. , Jain Barbie , Knight Erik L. , Roos Leslie E. , Giuliano Ryan J.
Published: July 2023

Objective

Heart rate is a transdiagnostic correlate of affective states and the stress diathesis model of health. Although most psychophysiological research has been conducted in laboratory environments, recent technological advances have provided the opportunity to index pulse rate dynamics in real-world environments with commercially available mobile health and wearable photoplethysmography (PPG) sensors that allow for improved ecologically validity of psychophysiological research. Unfortunately, adoption of wearable devices is unevenly distributed across important demographic characteristics, including socioeconomic status, education, and age, making it difficult to collect pulse rate dynamics in diverse populations. Therefore, there is a need to democratize mobile health PPG research by harnessing more widely adopted smartphone-based PPG to both promote inclusivity and examine whether smartphone-based PPG can predict concurrent affective states.

Methods

In the current preregistered study with open data and code, we examined the covariation of smartphone-based PPG and self-reported stress and anxiety during an online variant of the Trier Social Stress Test, as well as prospective relationships between PPG and future perceptions of stress and anxiety in a sample of 102 university students.

Results

Smartphone-based PPG significantly covaries with self-reported stress and anxiety during acute digital social stressors. PPG pulse rate was significantly associated with concurrent self-reported stress and anxiety (b = 0.44, p = .018) as well as prospective stress and anxiety at the subsequent time points, although the strength of this association diminished the farther away pulse rate got from self-reported stress and anxiety (lag 1 model: b = 0.42, p = .024; lag 2 model: b = 0.38, p = .044).

Conclusions

These findings indicate that PPG provides a proximal measure of the physiological correlates of stress and anxiety. Smartphone-based PPG can be used as an inclusive method for diverse populations to index pulse rate in remote digital study designs.
The Accuracy of Nonstandardized MELD/PELD Score Exceptions in the Pediatric Liver Allocation System
Authors: Ahn Daniel J. , Zeng Sharon , Pelzer Kenley M. , Barth Rolf N. , Gallo Amy , Parker William F.
Published: July 2023

Background.

In the United States, over half of pediatric candidates receive exceptions and status upgrades that increase their allocation model of end-stage liver disease/pediatric end-stage liver disease (MELD/PELD) score above their laboratory MELD/PELD score. We determined whether these “nonstandardized” MELD/PELD exceptions accurately depict true pretransplant mortality risk.

Methods.

Using data from the Scientific Registry of Transplant Recipients, we identified pediatric candidates (<18 y of age) with chronic liver failure added to the waitlist between June 2016 and September 2021 and estimated all-cause pretransplant mortality with mixed-effects Cox proportional hazards models that treated allocation MELD/PELD and exception status as time-dependent covariates. We also estimated concordance statistics comparing the performance of laboratory MELD/PELD with allocation MELD/PELD. We then compared the proportion of candidates with exceptions before and after the establishment of the National Liver Review Board.

Results.

Out of 2026 pediatric candidates listed during our study period, 403 (19.9%) received an exception within a week of listing and 1182 (58.3%) received an exception before delisting. Candidates prioritized by their laboratory MELD/PELD scores had an almost 9 times greater risk of pretransplant mortality compared with candidates who received the same allocation score from an exception (hazard ratio 8.69; 95% confidence interval, 4.71-16.03; P < 0.001). The laboratory MELD/PELD score without exceptions was more accurate than the allocation MELD/PELD score with exceptions (Harrell’s c-index 0.843 versus 0.763). The proportion of patients with an active exception at the time of transplant decreased significantly after the National Liver Review Board was implemented (67.4% versus 43.4%, P < 0.001).

Conclusions.

Nonstandardized exceptions undermine the rank ordering of pediatric candidates with chronic liver failure.
Acute hemorrhagic necrotizing encephalopathy associated with COVID-19 in a patient with liver cirrhosis
Authors: Singh Sweta , Singh Uday Shanker
Published: July 2023

COVID-19 emerging as a global pandemic is a complex disease presenting with multiorgan involvement.AHNE is a rarely reported phenomenon post COVID-19 infection but is a rapidly progressing, fatal, haemorrhagic necrosis of the CNS parenchyma. Here,we present a very interesting case of a cirrhotic male patient with acute hemorraghic necrotizing encephalopathy with COVID-19 infection. Diagnosis of AHNE requires a multimodality approach and high index of suspicion in a patient suffering from SARS CoV-2.Timely intervention and diagnosis may lead to a favourable outcome in the diagnosed cases.Future detailed studies in this direction may give an insight on this rare but important disease entity.
Position Statement: Exercise Guidelines for Osteoporosis Management and Fall Prevention in Osteoporosis Patients
Authors: Bae Seongryu , Lee Seungyong , Park Hyuntae , Ju Yongin , Min Seok-Ki , Cho Jinkyung , Kim Hyojin , Ha Yong-Chan , Rhee Yumie , Kim Young-Pyo , Kim Changsun
Published: July 2023

Background: The effectiveness of exercise for improving osteoporosis and fall prevention in patients diagnosed with osteoporosis or osteopenia has not been fully summarized. The Korean Society for Bone and Mineral Research and the Korean Society of Exercise Physiology has developed exercise guidelines for patients with osteoporosis or osteopenia and provide evidence-based recommendations.Methods: A systematic review identified randomized controlled trials (RCT) assessing the effect of resistance, impact, balance, aerobic training, and physical activity in osteoporosis and osteopenia on bone quality, physical performance, quality of life, and fall prevention. PubMed, Embase, KoreaMed, and RISS were searched from January 2000 to August 2022. Ten key questions were established to review the evidence and formulate recommendations.Results: The 50 RCTs reported that even with osteoporosis and osteopenia, resistance and impact training consistently maximized bone strength, improved body strength and balance, and eventually reduced fall incidences. Resistance exercise combining 3 to 10 types of free weight and mechanical exercise of major muscle groups performed with an intensity of 50% to 85% 1-repetition maximum, 5 to 12 repetitions/set, 2 to 3 days/week, for 3 to 12 months is recommended. Impact exercises such as jumping chin-ups with drop landings and jump rope performed 50 jumps/session for at least 6 months with 3 or more days/week are recommended.Conclusions: A multi-component exercise mainly comprised of resistance and impact exercise seems to be an effective strategy to attenuate the risk factors of osteoporosis and osteopenia. The integration of exercise guidelines and individualized exercise plans has significant potential to reduce the morbidity and mortality of osteoporosis.
Effects of Bazedoxifene/Vitamin D Combination Therapy on Serum Vitamin D Levels and Bone Turnover Markers in Postmenopausal Women with Osteopenia: A Randomized Controlled Trial
Authors: Jeong Chaiho , Ha Jeonghoon , Yoo Jun-Il , Lee Young-Kyun , Kim Jung Hee , Ha Yong-Chan , Min Yong-Ki , Byun Dong-Won , Baek Ki-Hyun , Chung Ho Yeon
Published: July 2023

Background: This study aimed to evaluate the effectiveness of bazedoxifene/vitamin D combination therapy in preventing osteoporosis in postmenopausal women with osteopenia.Methods: This was an open-label, multicenter randomized-controlled, phase 4 clinical trial. Women between ages of 55 and 70 years in 9 medical tertiary centers in Korea were enrolled and assigned into 2 groups: an experiment group and a control group. The experimental group received bazedoxifene 20 mg/vitamin D 800 IU tablets for 6 months, and the control group received calcium 100 mg/vitamin D 1,000 IU tablets for 6 months.Results: A total of 142 patients (70 in the experimental group and 72 in the control group) were included. The least-square mean±standard error of change in propeptide of type I collagen after 3 months was -6.87±2.56% in the experimental group and 1.22±2.54% in the control group. After 6 months, it was -21.07±2.75% in the experimental group and 1.26±2.71% in the control group. The difference between the 2 groups was -22.33% (p<0.01). The change of C-terminal telopeptide was -12.55±4.05% in the experimental group and 11.02±4.03% in the control group after 3 months. It was -22.0±3.95% and 10.20±3.89, respectively, after 6 months. The difference between the 2 groups was -32.21% (p<0.01) after 6 months. There was no significant difference in adverse events between the 2 groups.Conclusions: The osteoporosis preventive effect and safety of administering bazedoxifene/vitamin D combination pill were confirmed in postmenopausal women who needed osteoporosis prevention.
A Rare Case of Hyperfunctioning Lipoadenoma Presenting as a Cystic Pararthyroid Lesion
Authors: Kim Jinyoung , Kwon Ohjoon , Kim Tae-Jung , Jung So Lyung , Han Eun Ji , Song Ki-Ho
Published: July 2023

A 58-year-old woman visited the hospital complaining of fatigue and indigestion lasting for more than 3 months. She had no medical history other than taking a calcium plus vitamin D supplement for osteopenia. The initial blood test showed a high calcium level of 14.0 mg/dL. Additional tests were performed to differentially diagnose hypercalcemia. The blood test results were as follows: serum parathyroid hormone (PTH)=247.0 pg/mL, PTH-related peptide <1.0 pg/mL, phosphorous=2.6 mg/dL, 25-hydroxy-vitamin D=14.5 pg/mL, creatinine=1.09 mg/dL, and 24 hr urine calcium=215 mg/dL. A 4.5 cm sized cystic lesion on the intra-thyroidal space was confirmed on neck sonography and 4-dimensional parathyroid computed tomography, but technetium-99m methoxyisobutylisonitrile parathyroid scintigraphy showed equivocal results. After removal of the cystic lesion, serum calcium and PTH were normalized, and parathyroid lipoadenoma was confirmed in the postoperative pathology. Clinical features of parathyroid lipoadenoma are known to be similar to common parathyroid adenoma, but imaging studies often report negative findings. Therefore, it is necessary to better understand this rare disease for the differential diagnosis. For the final diagnosis and treatment of this disease, parathyroidectomy with intraoperative PTH measurement may be required.
Uncharacterized yeast geneYBR238C,an effector of TORC1 signaling in a mitochondrial feedback loop, accelerates cellular aging viaHAP4- andRMD9-dependent mechanisms
Authors: Alfatah Mohammad , Lim Jolyn Jia Jia , Zhang Yizhong , Naaz Arshia , Trishia Cheng Yi Ning , Yogasundaram Sonia , Faidzinn Nashrul Afiq , Jovian Jing Lin , Eisenhaber Birgit , Eisenhaber Frank
Published: July 2023

Uncovering the regulators of cellular aging will unravel the complexity of aging biology and identify potential therapeutic interventions to delay the onset and progress of chronic, aging-related diseases. In this work, we systematically compared gene sets involved in regulating the lifespan ofSaccharomyces cerevisiae(a powerful model organism to study the cellular aging of humans) and those with expression changes under rapamycin treatment. Among the functionally uncharacterized genes in the overlap set,YBR238Cstood out as the only one downregulated by rapamycin and with an increased chronological and replicative lifespan upon deletion. We show thatYBR238Cand its paralogueRMD9oppositely affect mitochondria and aging.YBR238Cdeletion increases the cellular lifespan by enhancing mitochondrial function. Its overexpression accelerates cellular aging via mitochondrial dysfunction. We find that the phenotypic effect ofYBR238Cis largely explained byHAP4- andRMD9-dependent mechanisms. Further, we find that genetic or chemical-based induction of mitochondrial dysfunction increases TORC1 (Target of Rapamycin Complex 1) activity that, subsequently, accelerates cellular aging. Notably, TORC1 inhibition by rapamycin (or deletion ofYBR238C) improves the shortened lifespan under these mitochondrial dysfunction conditions in yeast and human cells. The growth of mutant cells (a proxy of TORC1 activity) with enhanced mitochondrial function is sensitive to rapamycin whereas the growth of defective mitochondrial mutants is largely resistant to rapamycin compared to wild type. Our findings demonstrate a feedback loop between TORC1 and mitochondria (theTORC1-MItochondria-TORC1 (TOMITO) signaling process) that regulates cellular aging processes. Hereby,YBR238Cis an effector of TORC1 modulating mitochondrial function.
Anti-muscle Atrophy Effects ofLactobacillus reuteriATG-F4 and Its Impact on Intestinal Microbiota and Metabolites: Implications for Prophylaxis and Therapy
Authors: Lee Daeyoung , Lee Young-Sil , Park Gun-Seok , Park Juyi , Ko Seung-Hyun , Lee You-Kyung , Jeong Do Yeun , Lee Yong Hyun , Kang Jihee
Published: July 2023

Lactobacillus reuteriATG-F4, human gut-derived bacteria, was orally administrated in a model of hindlimb immobilization and confirmed the muscular performance, muscle mass and mechanism on anti-atrophy study. Concomitantly, the changes in the intestinal flora, the metabolites and cytokines were investigated. In the stapled immobilization mice model, ATG- F4 treated group had significantly increased muscle mass, myofiber size, running time to be exhausted and grip strength. The cytokine levels in serum and muscle tissues were reduced by ATG-F4 treatment. Furthermore, the phosphorylation of proteins involved in muscle synthesis such as mTOR, p70S6K, rpS6 and 4E-BP1 increased and MuRF1 related to muscle atrophy factor reduced in the TA and GA muscles. ATG-F4 treatment changed the ratio of main intestinal microflora by increasing the family Muribaculaceae (phylum Bacteroidetes) and decreasing the family Lachnospiraceae (phylum Firmicutes) and Lactobacillaceae (phylum Firmicutes). Also, the level of short chain fatty acids (SCFAs) including butyric acid and acetic acid in the serum of ATG-F4 group were increased. These results suggest thatL. reuteriATG- F4 can inhibit muscle atrophy and it is associated with the microbiota and its metabolites with the anti-inflammation effect. ATG-F4 may be a potential prophylactic or therapeutic composition for muscle atrophy.
Recyclable CRISPR/Cas9 mediated gene disruption and deletions inHistoplasma
Authors: Joehnk Bastian , Ali Nebat , Voorhies Mark , Walcott Keith , Sil Anita
Published: July 2023

Targeted gene disruption is challenging in the dimorphic fungal pathogenHistoplasmadue to the low frequency of homologous recombination. Transformed DNA is either integrated ectopically into the genome or maintained extra chromosomally byde novoaddition of telomeric sequences. Based on a system developed inBlastomyces, we adapted a CRISPR/Cas9 system to facilitate targeted gene disruption inHistoplasmawith high efficiency. We express a codon-optimized version of Cas9 as well as guide RNAs from a single ectopic vector carrying a selectable marker. Once the desired mutation is verified, one can screen for isolates that have lost the Cas9 vector by simply removing the selective pressure. Multiple mutations can then be generated in the same strain by retransforming the Cas9 vector carrying different guides. We used this system to disrupt a number of target genes includingRYP2andSRE1where loss-of-function mutations could be monitored visually by colony morphology or color, respectively. Interestingly, expression of two guide RNAs targeting the 5’ and 3’ ends of a gene allowed isolation of deletion mutants where the sequence between the guide RNAs was removed from the genome. Whole-genome sequencing showed that the frequency of off-target mutations associated with the Cas9 nuclease was negligible. Finally, we increased the frequency of gene disruption by using an endogenousHistoplasmaregulatory sequence to drive guide RNA expression. These tools transform our ability to generate targeted mutations inHistoplasma.

Importance

Histoplasmais a primary fungal pathogen with the ability to infect otherwise healthy mammalian hosts, causing systemic and sometimes life-threatening disease. Thus far, molecular genetic manipulation of this organism has utilized RNA interference, random insertional mutagenesis, and a homologous recombination protocol that is highly variable and often inefficient. Targeted gene manipulations have been challenging due to poor rates of homologous recombination events inHistoplasma. Interrogation of the virulence strategies of this organism would be highly accelerated by a means of efficiently generating targeted mutations. We have developed a recyclable CRISPR/Cas9 system that can be used to introduce gene disruptions inHistoplasmawith high efficiency, thereby allowing disruption of multiple genes.
Dissecting components of theCampylobacter jejuni fetMP-fetABCDEFgene cluster in iron scavenging
Authors: Richardson-Sanchez Tomas , Chan Anson C. K. , Sabatino Brendil , Lin Helen , Gaynor Erin C. , Murphy Michael E. P.
Published: July 2023

Campylobacter jejuniis a leading cause of bacterial gastroenteritis worldwide. Acute infection can be antecedent to highly debilitating long-term sequelae. Expression of iron acquisition systems is vital forC. jejunito survive the low iron availability within the human gut. TheC. jejuni fetMP-fetABCDEFgene cluster is known to be upregulated during human infection and under iron limitation. While FetM and FetP have been functionally linked to iron transport in prior work, here we assess the contribution by each of the downstream genes (fetABCDEF) toC. jejunigrowth during both iron-depleted and iron-replete conditions. Significant growth impairment was observed upon disruption offetA,fetB, fetC, andfetD, suggesting a role in iron acquisition for each encoded protein. FetA expression was modulated by iron-availability but not dependent on the presence of FetB, FetC, FetD, FetE or FetF. Functions of the putative thioredoxins FetE and FetF were redundant in iron scavenging, requiring a double deletion (ΔfetEF) to exhibit a growth defect.C. jejuniFetE was expressed and the structure solved to 1.50 Å, revealing structural similarity to thiol-disulfide oxidases. Functional characterization in biochemical assays showed that FetE reduced insulin at a slower rate thanE. coliTrx and that together, FetEF promoted substrate oxidation in cell extracts, suggesting that FetE (and presumably FetF) are oxidoreductases that can mediate oxidationin vivo. This study advances our understanding of the contributions by thefetMP-fetABCDEFgene cluster to virulence at a genetic and functional level, providing foundational knowledge towards mitigatingC. jejuni-related morbidity and mortality.
Single transcript-level metabolic responsive landscape of human liver transcriptome
Authors: Jiang Chengfei , Li Ping , Ma Yonghe , Yoneda Nao , Nishiwaki Megumi , Ohnishi Yasuyuki , Suemizu Hiroshi , Cao Haiming
Published: July 2023

Direct knowledge of gene regulation in human liver by metabolic stimuli could fundamentally advance our understanding of metabolic physiology. This information, however, is largely unknown, and this void is deeply rooted in a paradox that is caused by the inaccessibility of human liver to treatments and the insufficient annotation of liver transcriptome. Recent advances have uncovered immense complexity of transcriptome, i.e., multiple transcripts produced from one gene and extensive RNA modifications, which are all highly regulated and often condition-dependent. Establishing an inclusive annotation to study liver transcriptome dynamics thus requires human liver samples of diverse conditions, which are paradoxically unavailable due to the inaccessibility of human liver to treatments. In this work, we addressed these challenges by coupling an isogenic humanized mouse model with Nanopore single-molecule direct RNA sequencing (DRS). We first generated mice that carried humanized livers of identical genetic background, which were equivalent to clones of a single human liver, and then subjected the mice to representative metabolic treatments. We then analyzed the humanized livers with Nanopore DRS, which directly reads full-length native RNAs to determine the expression level, m6A modification and poly(A) tail length of all RNA transcript isoforms. Thus, our system allows for constructing a de novo annotation of human liver transcriptomes reflecting metabolic responses and studying transcriptome dynamics in conjunction. Our analysis uncovered a vast number of novel genes and transcripts that have not been previously reported. Our transcript-level analysis of human liver transcriptomes also identified a multitude of regulated metabolic pathways that were otherwise invisible using conventional short read RNA-seq. We also revealed for the first time the dynamic changes in m6A and poly(A) tail length of human liver transcripts many of which are transcribed from key metabolic genes. Furthermore, we performed comparative analyses of gene regulation between human and mouse and between two individuals using the liver-specific humanized mice. This revealed that transcriptome dynamics are highly species- and genetic background-dependent, which may only be faithfully studied in a humanized system that entails clones of the same human liver. Hence our work revealed a complex metabolic responsive landscape of human liver transcriptome and also provided a framework to understand transcriptome dynamics of human liver in response to physiologically relevant metabolic stimuli.
Biologically plausible gated recurrent neural networks for working memory and learning-to-learn
Authors: van den Berg Alexandra R. , Roelfsema Pieter R. , Bohte Sander M.
Published: July 2023

The acquisition of knowledge does not occur in isolation; rather, learning experiences in the same or similar domains amalgamate. This process through which learning can accelerate over time is referred to as learning-to-learn or meta-learning. While meta-learning can be implemented in recurrent neural networks, these networks tend to be trained with architectures that are not easily interpretable or mappable to the brain and with learning rules that are biologically implausible. Specifically, these rules employ backpropagation-through-time for learning, which relies on information that is unavailable at synapses that are undergoing plasticity in the brain. While memory models that exclusively use local information for their weight updates have been developed, they have limited capacity to integrate information over long timespans and therefore cannot easily learn-to-learn. Here, we propose a novel gated recurrent network named RECOLLECT, which can flexibly retain or forget information by means of a single memory gate and biologically plausible trial-and-error-learning that requires only local information. We demonstrate that RECOLLECT successfully learns to represent task-relevant information over increasingly long memory delays in a pro-/anti-saccade task, and that it learns to flush its memory at the end of a trial. Moreover, we show that RECOLLECT can learn-to-learn an effective policy on a reversal bandit task. Finally, we show that the solutions acquired by RECOLLECT resemble how animals learn similar tasks.
The effects of performance measurement on megaproject performance: the moderating effects of project complexity
Authors: Lin Wensheng , Wang Guangbin , Ning Yan , Ma Qiuwen , Dai Shuyuan
Published: July 2023

Purpose

Megaproject performance measurement (MPM) has received great attention in the project management community, but it primarily focused on the design of performance measures or frameworks. Yet, whether MPM utilization can improve megaproject performance and how project actors use MPM to improve megaproject performance is less well understood. This study aims to investigate whether and how the use of MPM can contribute to better megaproject performance.

Design/methodology/approach

Through the lens of the lever of control, this study conceptualizes MPM utilization as diagnostic use and interactive use. A holistic research model and related hypotheses integrating MPM use, project complexity and megaproject performance were established. The model was validated using a partial square-structural equation modeling method.

Findings

Based on 214-megaproject data collected through a questionnaire survey in China, the results show positive effects of diagnostic use and interactive use on megaproject performance. Both, however, have substitutional interaction effects. The moderating results suggest that the higher project complexity weakens the positive effects of MPM utilization on megaproject performance.

Originality/value

This study advances megaprojects performance measurement and management literature by validating the value of MPM utilization on performance. It also presents practical implications for project managers to improve performance by appropriate MPM utilization.
Students' sound environment perceptions in informal learning spaces: a case study on a university campus in Australia
Authors: Zhang Jia , Liu Chunlu , Luther Mark , Chil Brian , Zhao Jilong , Liu Changan
Published: July 2023

Purpose

Physical environments, especially the sound environments of ILSs on a university campus, have become increasingly important in satisfying the diverse needs of students. Poor sound environments are widely acknowledged to lead to inefficient and underutilised spaces and to negatively influence students' learning outcomes. This study proposes two hypotheses to explore whether students' sound environment perceptions are related to their individual characteristics and whether students' preferences for the type of ILS are related to their sound environment sensitivities.

Design/methodology/approach

An investigation through a questionnaire survey has been conducted on both students' individual characteristics affecting their sound environment perceptions in informal learning spaces (ILSs) of a university campus and their sensitivities to the sound environments in ILSs affecting their preferences for the type of ILSs.

Findings

The research findings indicate that students' sound environment perceptions are associated with some of their individual characteristics. In addition, the results show that students' sound environment sensitivities affect their preferences for the type of ILS they occupy.

Originality/value

This study could help architects and managers of university learning spaces to provide better sound environments for students, thereby improving their learning outcomes. The article contributes valuable insights into the correlation between students' individual characteristics, sound environment perceptions and preferences for ILSs. The research findings add to the existing knowledge in this field and offer practical implications for enhancing design and management of university learning environments.
Layers of love – exploring the interactive layers of brand love in the social media setting
Authors: Aro Kaisa , Suomi Kati , Gyrd-Jones Richard
Published: July 2023

Purpose

This study aims to add to the understanding of the interactive nature of brand love by using a multilayer perspective that incorporates individual, group and societal contexts.

Design/methodology/approach

The qualitative empirical study uses abductive reasoning. Its theories and conclusions are grounded in naturally occurring data from an online brand community. The approach revealed new interactive processes of brand love.

Findings

This study extends our understanding of the interactive nature of brand love by adopting a layered perspective incorporating micro- (individual), meso- (in-group), macro- (in-group vs out-group) and mega-layer (societal) social dynamics that complements the predominant focus on individual psychological processes. It challenges the linear, monodirectional trajectory approach to brand love, suggesting that brand love is in constant flux as individuals move across the layers in their identification with the brand.

Research limitations/implications

This study provides data from one destination brand in Finland. Future studies could consider other types of brands and contexts in other countries and cultures.

Practical implications

This study shows brand managers that brand lovers can be divided into subgroups with distinct drivers of their love to which brand managers should attend.

Originality/value

To the best of the authors’ knowledge, this is the first attempt to describe the interactive nature of brand love through interactions between and within four layers of brand love. Furthermore, this study enhances our understanding of the contradictory aspects of brand love.
Moderating role of collaborative technologies on the relationship between virtual knowledge sharing and team effectiveness: lessons from COVID-19
Authors: Farooq Rayees , Bashir Makhmoor
Published: July 2023

Purpose

This study aims to test the relationship between virtual knowledge sharing (VKS) and team effectiveness (TE) during the COVID-19 pandemic. The study also explores the moderating role of collaborative technologies.

Design/methodology/approach

This is a cross-sectional study conducted in the service sector of India. A purposive sample of 321 knowledge workers from National Capital Region of India was used. Questionnaires were distributed to knowledge workers working in a virtual environment. The hypotheses were tested with confirmatory factor analysis and structural equation modeling (SEM) using partial least square-SEM.

Findings

The study reveals that, amid the COVID-19 pandemic, virtual knowledge sharing (VKS) positively affects team effectiveness (TE). Furthermore, the impact of VKS on TE is contingent upon the utilization of collaborative technologies.

Originality/value

The study contributes to the existing literature by exploring the impact of VKS on TE during the COVID-19 pandemic and the importance of collaborative technologies in facilitating virtual team collaboration, which has practical implications for organizations seeking to enhance TE in virtual environments.