bluuebunny/crossref_metadata_2025 huggingface dataset:
O204: The influence of HLA matching on graft survival in lung transplant recipients is indication specific: An UNOS database analysis
Authors: Otunla Afolarin , Shanmugarajah Kumaran , Mukhtar Ghazel , Nabulsi Sarah , Dolan Daniel , Salciccioli Justin , Marshall Dominic , Madariaga Maria , Shalhoub Joseph
Published: March 2024

Background and aims

The importance of human leukocyte antigen (HLA) matching in lung transplantation remains unclear, and the influence of indication in HLA compatibility is unknown. This study aimed to determine the relationship between HLA matching and lung graft survival using a large-scale multi-center database (UNOS/OPTN) and multivariate logistic analysis. The secondary aim was to determine whether this relationship was influenced by transplant indication.

Methods

This retrospective observational analysis was performed using 26,312 lung transplant recipients from the UNOS/OPTN database. Patients were divided into two groups based on number of HLA mismatches (0-3 mismatches vs 4-6 mismatches) and then subcategorized by indication. Risk-adjusted outcomes were assessed by multivariate Cox analysis adjusting for donor and recipient characteristics and visualized using Kaplan-Meier survival curves.

Results

Increased HLA mismatch was associated with reduced allograft survival. Adjusted models found that the total HLA mismatch >3 increased the mortality hazard at 15 years (HR 1·05, p <0·05) and 20 years (HR 1·05, p<0·01). Pulmonary hypertension was the only indication with a statistically significant association between HLA mismatch and graft survival. Allografts in patients with 0-3 mismatches survived for 401 days longer than those with 4-6 mismatches (p=0·02).

Conclusion

Increased HLA mismatch reduced graft survival. When stratified by indication, this association was preserved exclusively in pulmonary hypertension. This finding is of potential clinical relevance to the management of this subsection of lung transplant recipients, impacting organ allocation, transplant surveillance and use of desensitisation and immunosuppression protocols.
O196: Gallbladder Necrosis: Predictive Factors in Patients Undergoing Emergent Cholecystectomy
Authors: Maharajh Sandeep , Brown Joshua , Chmelo Jakub , Phillips Alexander
Published: March 2024

Introduction

Gallstones are present in up to 25% of the general population and approximately 2% of these become symptomatic. Gallbladder necrosis is a complication of gallstones associated with higher risks of morbidity and mortality. Identification of risk factors which portend to gallbladder necrosis is key in prioritising investigation and treatment for higher risk patients.

Method

A retrospective review of all patients undergoing emergency cholecystectomy in a tertiary hospital over a 2-year period was performed. Gallbladder necrosis was diagnosed on histopathological examination of operative specimens. Multivariable logistic regression was performed to determine risk factors for gallbladder necrosis.

Results

152 patients underwent acute cholecystectomy and 44 (29%) had proven gallbladder necrosis. Multivariable model demonstrated that white cell count (WCC) (OR 1.122, 95% CI 1.031-1.221, p=0.007), C-reactive protein (CRP) (OR 1.004, 95% CI 1.001-1.008, p=0.022) and smoking status (OR 5.724, 95% CI 1.323-24.754, p=0.020) were independently predictive of gallbladder necrosis. Notably, advancing age, elevated BMI, diabetes mellitus or ASA grade were not found to be associated with developing necrosis.

Conclusion

Patients at risk of gallbladder necrosis include those with higher WCC, CRP and active smokers. Given the increased potential complications, these risk factors should be identified early in the management of those admitted with gallstone disease to ensure such patients receive aggressive medical therapy alongside timely and guided surgical intervention.
O93: Calcium channel blockers are associated with improved survival in pancreatic cancer patients undergoing neoadjuvant chemotherapy and resection
Authors: Fong Zhi , Severs George , Moir John , White Steve , Qadan Motaz , Tingle Samuel
Published: March 2024

Background

Repurposing existing drugs for use in oncology is more safe, efficient and cost-effective than novel drug discovery. Calcium signalling is increasingly recognised to have a key role in chemoresistance and many of the hallmarks of cancer. This study aims to assess the impact of calcium channel blockers (CCB) in pancreatic cancer.

Methods

Retrospective population study including patients in the SEER-Medicare linked database who underwent resection with curative intent of pancreatic ductal adenocarcinoma diagnosed between 2007 and 2017. Adjusted cox regression models were built to assess the impact on overall survival. As laboratory studies suggest a chemosensitising effect, we assessed the impact of CCB separately in patients receiving chemotherapy.

Results

6,223 patients were included, of whom 660 were prescribed CCB. 591 patients received neoadjuvant chemotherapy prior to resection; in this cohort CCB prescription was associated with a significant improvement in overall survival when adjusting for multiple prognostic factors (aHR=0.715, 0.514-0.996, P=0.047). This effect was not observed in patients who did not receive neoadjuvant chemotherapy (aHR=1.082, 0.982-1.191, P=0.112), or in the overall cohort (aHR=1.056, 0.963-1.158, P=0.248), suggesting a chemosensitising effect.

Discussion

CCB prescription was associated with improved overall survival in patients receiving neoadjuvant chemotherapy prior to pancreatic cancer resection. The association was specific to the group of patients receiving neoadjuvant chemotherapy. This indicates a chemosensitising effect of CCB, which mirrors previous laboratory studies. This study defines those receiving neoadjuvant chemotherapy as a target population for prospective clinical trials of CCB in pancreatic cancer.
P35: A Systematic review on the outcomes of the reverse shoulder arthroplasty versus hemiarthroplasty for the 3- and 4- part proximal humeral fractures in the elderly population
Authors: Syziu Anxhela , Brooks-Fazakerley Steven
Published: March 2024

Background

The hemiarthroplasty (HA) and reverse total shoulder arthroplasty (RTSA) are common surgical methods in of the proximal humerus management, where the surgical fixation is not feasible. Our aim is to analyse the most recent data to inform choices on best management for managing 3- and 4 -part fracture dislocations of the proximal humeral fractures in the elderly population.

Methods

The Medline, PubMed and Scopus databases were searched in line with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines to identify the relevant literature to include for analysis. The inclusion criteria involved English language, functional outcomes, revision rates, hemiarthroplasty, and reverse total shoulder arthroplasty. The exclusion criteria were publications before 2018, systematic reviews and meta-analysis, other management options such as conservative management, surgical fixation, and total anatomical shoulder replacement.

Results

The data collected included study design and level of evidence, number of patients and patients’ characteristics, follow-up time post-surgery, functional outcomes, range of movement, Constant score, subjective scores including Disability of Arm and Shoulder (QuickDASH) and American Shoulder and Elbow Score (ASES), and revision rates.

Conclusions

The evidence suggests that RTSA is the new gold standard management for 3- and 4-part fracture dislocations of the proximal humerus in a selected group of patients over 65 years old with irreparable rotator cuff. The available literature is medium quality, requiring more robust evidence including prospective large cohort studies utilising unified objective and subjective functional outcome scores.
P230: The challenges of implementing early surgery for terminal ileal Crohn’s disease – a qualitative study of the clinician perspective
Authors: Husnoo Nilofer , Morgan Jenna L , Wyld Lynda , Brown Steven R
Published: March 2024

Background

Recent evidence suggests that “early” bowel resection may offer more stable remission in terminal ileal (TI) Crohn’s disease compared to medical therapy. Surgery is still often considered late in the treatment pathway. The aims of this study were to understand how clinicians make decisions about treatment for TI Crohn's and to explore their views on the role of surgery.

Methods

Semi-structured interviews with clinicians across the UK, with an interest in inflammatory bowel disease (IBD), were undertaken using videoconferencing (February to November 2022). Inductive thematic analysis was performed and 10% of the data were double-coded. Data saturation was confirmed before stopping recruitment.

Results

Participants included 9 consultant surgeons, 7 consultant gastroenterologists and 7 specialist nurses (n=23) from secondary care and tertiary referral centres. Five key themes were identified: approach to management and decision-making, opinions on medical therapy, opinions on surgery, approach to information-giving, and patients’ preferences from a clinician perspective. Symptoms, disease phenotype, patient choice and the influence of the IBD multidisciplinary team were frequently discussed factors that guide management. Trial of multiple drugs before offering surgery was commonly described. A lack of IBD surgeons and long waiting lists for surgical clinics and theatre were cited as barriers to timely surgery. Patients' fear of surgery was thought to be driven by the risk of a stoma.

Conclusion

This study highlights key barriers to early surgery for TI disease. Early discussion of surgery may allow patients to make an informed choice. Organisational barriers should be considered when designing local services.
P261: Metaverse gamified aesthetic education – a think-aloud usability pilot study
Authors: Zargaran Alexander , Zargaran David , Sousi Sara , Mosahebi Afshin
Published: March 2024

Introduction

Ten years on from the Keogh Review of cosmetic surgery in the UK, improvements in training and education are yet to be achieved. Gamified learning and metaverse technology have been posited as transformational media for learning. This study evaluates the usability of a metaverse gamified platform for aesthetic education.

Methods

An aesthetic education platform for administration of Botulinum Toxin was developed in Unity Game Engine. Qualitative semi-structured interviews were conducted using Nielsen’s (1994) usability testing of end-users, combining task-based assessment with free exploration of the platform. Articulated thoughts were transcribed, whilst the platform was screen recorded. Verbal and observational data were thematically analysed and coded, whilst barriers and facilitators were rated on a modified Likert scale.

Results

A total of eight medical students and junior doctors were included in the study. Six higher themes were developed including aesthetic interface, familiarity, coherence, interactivity, ease of use and utility. Coherence and interactivity were identified as the most potent drivers of learning, whilst familiarity and aesthetic interface were the biggest potential barriers.

Conclusion

A metaverse gamified educational platform in aesthetic plastic surgery is potentially usable and useful for doctors and medical students as a learning tool. Important facilitators include focus on in-game coherence and interactivity. Further work is needed to develop educational experiences further within metaverse settings in aesthetic plastic surgery to enhance education and promote patient safety.
Black ceiling tiles reduce occupational ultraviolet light exposure from phototherapy cabinets
Authors: Bajek David , Sharpe Katherine , Eadie Ewan
Published: March 2024

Phototherapy clinics administer ultraviolet (UV) light to patients using phototherapy cabinets. The UV radiation from these cabinets is reflected on the white ceiling tiles of the clinic and is then redirected toward both staff and patients in the area. This is particularly problematic for clinical technologists who must undertake dosimetry in these areas and have a specific time (often as low as 30 min) before they reach their maximum exposure limit. By replacing white tiles with black ones, which absorb any stray radiation, we were able to reduce stray reflection by almost 90%, prolonging the time to maximum exposure by nearly 10 times. We present these findings to encourage other similar clinics to undertake the simple protocols outlined in this article, which will significantly improve staff and patient safety.
High-level language brain regions process sublexical regularities
Authors: Regev Tamar I , Kim Hee So , Chen Xuanyi , Affourtit Josef , Schipper Abigail E , Bergen Leon , Mahowald Kyle , Fedorenko Evelina
Published: March 2024

A network of left frontal and temporal brain regions supports language processing. This “core” language network stores our knowledge of words and constructions as well as constraints on how those combine to form sentences. However, our linguistic knowledge additionally includes information about phonemes and how they combine to form phonemic clusters, syllables, and words. Are phoneme combinatorics also represented in these language regions? Across five functional magnetic resonance imaging experiments, we investigated the sensitivity of high-level language processing brain regions to sublexical linguistic regularities by examining responses to diverse nonwords—sequences of phonemes that do not constitute real words (e.g. punes, silory, flope). We establish robust responses in the language network to visually (experiment 1a, n = 605) and auditorily (experiments 1b, n = 12, and 1c, n = 13) presented nonwords. In experiment 2 (n = 16), we find stronger responses to nonwords that are more well-formed, i.e. obey the phoneme-combinatorial constraints of English. Finally, in experiment 3 (n = 14), we provide suggestive evidence that the responses in experiments 1 and 2 are not due to the activation of real words that share some phonology with the nonwords. The results suggest that sublexical regularities are stored and processed within the same fronto-temporal network that supports lexical and syntactic processes.
Perceiving and misperceiving speech: lexical and sublexical processing in the superior temporal lobes
Authors: Tolkacheva Valeriya , Brownsett Sonia L E , McMahon Katie L , de Zubicaray Greig I
Published: March 2024

Listeners can use prior knowledge to predict the content of noisy speech signals, enhancing perception. However, this process can also elicit misperceptions. For the first time, we employed a prime–probe paradigm and transcranial magnetic stimulation to investigate causal roles for the left and right posterior superior temporal gyri (pSTG) in the perception and misperception of degraded speech. Listeners were presented with spectrotemporally degraded probe sentences preceded by a clear prime. To produce misperceptions, we created partially mismatched pseudo-sentence probes via homophonic nonword transformations (e.g. The little girl was excited to lose her first tooth—Tha fittle girmn wam expited du roos har derst cooth). Compared to a control site (vertex), inhibitory stimulation of the left pSTG selectively disrupted priming of real but not pseudo-sentences. Conversely, inhibitory stimulation of the right pSTG enhanced priming of misperceptions with pseudo-sentences, but did not influence perception of real sentences. These results indicate qualitatively different causal roles for the left and right pSTG in perceiving degraded speech, supporting bilateral models that propose engagement of the right pSTG in sublexical processing.
Impact of sex and reproductive status on the default mode network in early midlife: implications for aging of memory circuitry and function
Authors: Spets Dylan S , Cohen Justine E , Konishi Kyoko , Aroner Sarah , Misra Madhusmita , Lee Hang , Goldstein Jill M
Published: March 2024

Alterations to the resting-state default mode network (rsDMN) are early indicators of memory decline and Alzheimer’s disease (AD). Brain regions shared by the rsDMN and memory circuitry are highly sexually dimorphic. However, data are limited regarding the impact of sex and reproductive status on rsDMN connectivity and memory circuitry and function. In the current investigation, rsDMN connectivity was assessed in 180 early midlife adults aged 45 to 55 by sex and reproductive status (87 women; 93 men). Associations between left and right hippocampal connectivity of rsDMN and verbal memory encoding circuitry were examined using linear mixed models, controlled for age and parental socioeconomic status, testing interactions by sex and reproductive status. Relative to men, women exhibited greater rsDMN connectivity between the left and right hippocampus. In relation to rsDMN-memory encoding connectivity, sex differences were revealed across the menopausal transition, such that only postmenopausal women exhibited loss of the ability to decrease rsDMN left–right hippocampal connectivity during memory encoding associated with poorer memory performance. Results demonstrate that sex and reproductive status play an important role in aging of the rsDMN and interactions with memory circuitry/function. This suggests the critical importance of sex and reproductive status when studying early midlife indicators of memory decline and AD risk.
Genome assembly of Genji firefly (Nipponoluciola cruciata) reveals novel luciferase-like luminescent proteins without peroxisome targeting signal
Authors: Fukuta Kentaro , Kato Dai-ichiro , Maeda Juri , Tsuruta Atsuhiro , Suzuki Hirobumi , Nagano Yukio , Tsukamoto Hisao , Niwa Kazuki , Terauchi Makoto , Toyoda Atsushi , Fujiyama Asao , Noguchi Hideki
Published: March 2024

The Genji firefly, Nipponoluciola cruciata, is an aquatic firefly endemic to Japan, inhabiting a wide area of the Japanese archipelago. The luminescence of fireflies is a scientifically interesting phenomenon, and many studies have evaluated this species in Japan. In this study, we sequenced the whole genome of male N. cruciata and constructed a high-quality genome assembly of 662 Mb with a BUSCO completeness of 99.1% in the genome mode. Using the detected set of 15,169 protein-coding genes, the genomic structures and genetic background of luminescence-related genes were also investigated. We found four new firefly luciferase-like genes in the genome. The highest bioluminescent activity was observed for LLa2, which originated from ancestral PDGY, a mitochondrial acyl-CoA synthetase. A thioesterase candidate, NcruACOT1, which is involved in d-luciferin biosynthesis, was expressed in the lantern. Two opsins were also detected and the absorption wavelength of the UV-type opsin candidate shifted from UV to blue. These findings provide an important resource for unravelling the adaptive evolution of fireflies in terms of luminescence and vision.
The process of ratifying the treaty to establish the African Medicines Agency: perspectives of national regulatory agencies
Authors: Ncube Bakani Mark , Dube Admire , Ward Kim
Published: March 2024

The vision of the African Medicines Agency (AMA) is to ensure that all Africans have access to affordable medical products that meet internationally recognized standards of quality, safety and efficacy for priority diseases/conditions. The AMA is being established by a treaty which had to be ratified by a minimum of 15 African countries. Although there was no deadline, the ratification process has been slower than expected. This study therefore analysed the rationale, perceived benefits, enabling factors and challenges of the AMA’s establishment. This study was a qualitative, cross-sectional, census survey of the national medicines regulatory authorities (NRAs) of 45 African countries. The Heads of NRAs and a senior NRA staff member were contacted to complete self-administered questionnaires. The existence of mature NRAs, the desire to have harmonized regulatory systems, the presence of strong political will and appropriate advocacy to expedite treaty signing are all enabling factors for AMA treaty signing. The challenges reported include the fact that the process is slow and there is limited understanding of the process. Competing national priorities, changes in office bearers in the public system and stagnation of the process at the ministerial level were also challenges reported. This study has improved the understanding of the treaty signing and ratification process and the perceived benefits and enabling factors of signing and ratification from African NRAs’ perspective. NRAs also highlighted challenges encountered in the process. Addressing these challenges will result in effective medicines regulation by galvanizing technical support, regulatory expertise and resources at a continental level.
Novel tetracycline resistance gene tet(65) located on a multi-resistance Corynebacterium plasmid
Authors: Kittl Sonja , Brodard Isabelle , Tresch Milena , Perreten Vincent
Published: March 2024

Background

Corynebacterium (C.) sp. 22KM0430 related to C. oculi and isolated from a dog exhibited resistance to tetracycline, and its WGS analysis revealed a putative resistance gene on a 35 562-bp plasmid also harbouring the MLSB resistance gene erm(X).

Objectives

To characterize the novel tetracycline resistance gene tet(65) and demonstrate its functionality by expression in C. glutamicum and Escherichia coli and plasmid curing of the host strain.

Methods

tet(65) was cloned with and without its repressor tetR(65) and expressed in C. glutamicum DSM20300 and E. coli DH5α. Plasmid was cured by non-selective passages. Minimal inhibitory concentrations (MICs) of tetracyclines were determined according to CLSI guidelines. Association of tet(65) with efflux was shown by the addition of reserpine to MIC assays. Phylogenetic position and transmembrane structure of Tet(65) were analysed using MEGA11 and DeepTMHMM.

Results

Tet(65) shows 73% amino acid identity with the closest related Tet(Z), contains 12 transmembrane domains and is structurally related to the Major Facilitator Superfamily. The tetracycline MICs decreased in the plasmid-cured strain and increased when tet(65) was expressed in C. glutamicum and in E. coli. The MICs of tetracycline decreased in the presence of reserpine indicating that tet(65) functions as an efflux pump. A GenBank search also identified tet(65) in C. diphtheriae and Brevibacterium (B.) casei and B. luteolum.

Conclusions

A novel tetracycline efflux gene tet(65) was identified in a C. oculi related species and was also present in the human pathogen C. diphtheriae and in Brevibacterium species indicating broader potential for dissemination.
Small area estimation of labour force indicators under unit-level multinomial mixed models
Authors: Bugallo María , Esteban María Dolores , Hobza Tomáš , Morales Domingo , Pérez Agustín
Published: March 2024

This paper presents a new statistical methodology for the small area estimation of the proportion of employed, unemployed and inactive people, and of unemployment rates. The novel empirical best and plug-in predictors are based on a multinomial mixed model that is fitted to unit-level data. Model parameters are estimated by maximum-likelihood and mean-squared errors by parametric bootstrap. Several simulation experiments are carried out to empirically investigate the properties of these estimators and predictors. Finally, a detailed application to real data from the first Spanish Labour Force Survey of 2021 is included, where the target is to map labour force indicators by province, sex, and age group.
Effect of textile colour on vector mosquito host selection: a simulated field study in Mali, West Africa
Authors: Benz Ursula , Traore Mohamad M , Revay Edita E , Traore Amadou S , Prozorov Alexey M , Traoré Issa , Junnila Amy , Cui Liwang , Saldaitis Aidas , Kone Aboubakr S , Yakovlev Roman V , Ziguime Younoussa , Gergely Petrányi , Samake Siriman , Keita Alou , Müller Günter C , Weitzel Thomas , Rothe Camilla
Published: March 2024

Background

The effect of clothing colour on the biting rates of different vector mosquito species is not well understood. Studies under tropical field conditions are lacking. This study aimed to determine the influence of clothing colours on mosquito biting rates in rural and suburban settings in West Africa.

Methods

We performed a simulated field study in a suburban and a rural site in Mali using Mosquito-Magnet traps utilizing CO2 and other attractants, which were covered with black, white, and black/white striped textile sheets covers. These targets operated continuously for 10 consecutive days with bright nights (around full moon) and 10 consecutive days with dark nights (around new moon). Trapped mosquitoes were collected and catch rates counted hourly. Mosquitoes were morphologically identified to the species complex level (Anopheles gambiae s.l. and Culex pipiens s.l.) or species level (Aedes aegypti). A subset of Anopheles specimens were further identified by molecular methods.

Results

Under bright-night conditions, An. gambiae s.l. was significantly more attracted to black targets than to white and striped targets; during dark nights, no target preference was noted. During bright nights, Cx. pipiens s.l. was significantly more attracted to black and striped targets than to white targets; a similar trend was noted during dark nights (not significant). For day-active Ae. aegypti, striped targets were more attractive than the other targets and black were more attractive than white targets.

Conclusions

The study firstly demonstrated that under field conditions in Mali, West Africa, mosquito catch rates were influenced by different clothing colours, depending on mosquito species and light conditions. Overall, light colours were least attractive to host-seeking mosquitoes. Using white or other light-coloured clothing can potentially reduce bite exposure and risk of disease transmission in endemic tropical regions.
The role of credit reports in digital lending: a case study from Mexico
Authors: Burlando Alfredo , Kuhn Michael A , Prina Silvia
Published: March 2024

Digital credit that uses non-traditional scoring techniques has already expanded credit access to many new populations. A point of policy debate is whether digital lenders should be fully integrated into information-sharing systems, such as those offered by credit reference bureaus (CRBs). We study an example of a digital lender in Mexico adopting credit bureau scores into its screening process. Using unique administrative data, we estimate a regression discontinuity in time around the lender’s integration of credit bureau scores. We find that the acquisition of credit scores reduces defaults, with the likelihood of borrowers’ repayment increasing by 10–13 per cent.
Fast growth and slow policy: a decade of digital credit in Kenya
Authors: Mazer Rafe , Garz Seth
Published: March 2024

The proliferation of mobile enabled instant credit products (digital credit) across emerging markets and developing economies poses challenges for policy-makers and practitioners that seek to expand access to credit while protecting consumers. The Kenya market, which experienced tremendous commercial innovation and growth from 2012 to 2022, but also significant consumer harms and unequal competition, offers a valuable reference case for actors in other markets facing rapid expansion of new fintech products and firms. Despite the substantial and often polarized debate around the country’s experience, there has been little systematic effort to capture and interpret key facts from the development of the digital credit market in Kenya during its first decade. This paper aims to fill that gap by providing a policy case study informed by original interviews of key stakeholders and extensive review of related academic and grey literature. The analysis suggests that policy responses were often inadequate to address the growing risks in Kenya’s digital credit market and presents five policy reflections from Kenya’s experience to support consumer protection and competition in emerging digital credit markets.
E3 SUMO ligase SIZ1 splicing variants localize and function according to external conditions
Authors: Kwak Jun Soo , Song Jong Tae , Seo Hak Soo
Published: March 2024

SIZ1 (SAP and MIZ1) is a member of the Siz/PIAS-type RING family of E3 SUMO (small ubiquitin-related modifier) ligases that play key roles in growth, development, and stress responses in plant and animal systems. Nevertheless, splicing variants of SIZ1 have not yet been characterized. Here, we identified four splicing variants of Arabidopsis (Arabidopsis thaliana) SIZ1, which encode three different protein isoforms. The SIZ1 gene encodes an 873-amino acid (aa) protein. Among the four SIZ1 splicing variants (SSVs), SSV1 and SSV4 encode identical 885 aa proteins; SSV2 encodes an 832 aa protein; and SSV3 encodes an 884 aa protein. SSV2 mainly localized to the plasma membrane, whereas SIZ1, SSV1/SSV4, and SSV3 localized to the nucleus. Interestingly, SIZ1 and all SSVs exhibited similar E3 SUMO ligase activities and preferred SUMO1 and SUMO2 for their E3 ligase activity. Transcript levels of SSV2 were substantially increased by heat treatment, while those of SSV1, SSV3, and SSV4 transcripts were unaffected by various abiotic stresses. SSV2 directly interacted with and sumoylated cyclic nucleotide-gated ion channel 6 (CNGC6), a positive thermotolerance regulator, enhancing the stability of CNGC6. Notably, transgenic siz1-2 mutants expressing SSV2 exhibited greater heat stress tolerance than wild-type plants, whereas those expressing SIZ1 were sensitive to heat stress. Furthermore, transgenic cngc6 plants overaccumulating a mutated mCNGC6 protein (K347R, a mutation at the sumoylation site) were sensitive to heat stress, similar to the cngc6 mutants, while transgenic cngc6 plants overaccumulating CNGC6 exhibited restored heat tolerance. Together, we propose that alternative splicing is an important mechanism that regulates the function of SSVs during development or under adverse conditions, including heat stress.
Online Exercise Programs for Chronic Nonspecific Neck Pain: A Randomized Controlled Trial Reveals Comparable Effects of Global, Local, and Combined Approaches
Authors: Bontinck Jente , Meeus Mira , Voogt Lennard , Chys Marjolein , Coppieters Iris , Cagnie Barbara , De Meulemeester Kayleigh
Published: March 2024

Objective

Specific neck exercises are recommended in the rehabilitation of chronic nonspecific neck pain (CNNP). They are unfortunately often accompanied by acute pain flare-ups. Global exercises might be a beneficial addition, as they activate endogenous analgesia without overloading painful structures. However, it is still unclear which type of exercise is most effective. This randomized controlled trial was done to evaluate the effect of an online blended program of global and specific neck exercises, compared to programs including only 1 of both types of exercise.

Methods

Forty-eight patients with CNNP were randomized into 3 groups. Online questionnaires were collected at baseline, at midtreatment, immediately after treatment, and at the 3-month follow-up. Quantitative sensory testing and actigraphy were assessed at baseline and after treatment. Linear mixed-model analyses were performed to evaluate treatment effects within and between groups. Neck pain–related disability after treatment was considered the primary outcome.

Results

No time × treatment interaction effects were found. All groups improved in neck pain–related disability, pain intensity, self-reported symptoms of central sensitization, local pain sensitivity, physical activity, and pain medication use. No effects were found on quality of life, sleep quality, depression, anxiety, stress, widespread pain sensitivity, health economics, or actigraphy measurements. A higher global perceived effect was reported after performing the blended program, compared to the other groups.

Conclusion

A blended exercise program was not superior to the stand-alone programs in reducing disability. Nevertheless, the global perceived effect of this type of exercise was higher. Future research necessitates larger sample sizes to adequately explore the optimal type of exercise for patients with CNNP.

Impact

Exercise therapy should be an important part of the rehabilitation of patients with CNNP, regardless of the type of exercise.
An Empirical Assessment of Characteristics and Optimal Portfolios
Authors: Lamoureux Christopher G , Zhang Huacheng
Published: March 2024

We implement a dynamically regularized, bootstrapped two-stage out-of-sample parametric portfolio policy to evaluate characteristics’ efficacy in the conditional stock return-generating process in the metric of expected power utility. Traditional characteristics, such as momentum and size afforded large utility gains before 1999. These opportunities have since vanished. Overfitting—imprecision in weight estimation—is correlated with the optimal portfolio’s variance. Therefore, it is not a problem for power utility investors with coefficients of relative aversion greater than four. For more risk-tolerant investors, we successfully reduce estimation error by increasing the curvature of the loss function relative to the investor’s utility function. (JEL L200; C110; C350)
Using Computational Phenotyping to Identify Divergent Strategies for Effort Allocation Across the Psychosis Spectrum
Authors: Whitton Alexis E , Cooper Jessica A , Merchant Jaisal T , Treadway Michael T , Lewandowski Kathryn E
Published: March 2024

Background and Hypothesis

Disturbances in effort-cost decision-making have been highlighted as a potential transdiagnostic process underpinning negative symptoms in individuals with schizophrenia. However, recent studies using computational phenotyping show that individuals employ a range of strategies to allocate effort, and use of different strategies is associated with unique clinical and cognitive characteristics. Building on prior work in schizophrenia, this study evaluated whether effort allocation strategies differed in individuals with distinct psychotic disorders.

Study Design

We applied computational modeling to effort-cost decision-making data obtained from individuals with psychotic disorders (n = 190) who performed the Effort Expenditure for Rewards Task. The sample included 91 individuals with schizophrenia/schizoaffective disorder, 90 individuals with psychotic bipolar disorder, and 52 controls.

Study Results

Different effort allocation strategies were observed both across and within different disorders. Relative to individuals with psychotic bipolar disorder, a greater proportion of individuals with schizophrenia/schizoaffective disorder did not use reward value or probability information to guide effort allocation. Furthermore, across disorders, different effort allocation strategies were associated with specific clinical and cognitive features. Those who did not use reward value or probability information to guide effort allocation had more severe positive and negative symptoms, and poorer cognitive and community functioning. In contrast, those who only used reward value information showed a trend toward more severe positive symptoms.

Conclusions

These findings indicate that similar deficits in effort-cost decision-making may arise from different computational mechanisms across the psychosis spectrum.
The Impact of Weather Shocks on Violent and Property Crimes in Jamaica
Authors: Wright Nicholas A , Stewart Aubrey M
Published: March 2024

Developing countries face the largest exposure to the negative effects of climate change. However, as temperature and rainfall patterns change, we have a limited understanding of their impact on these countries and the mitigation strategies that may be needed. In this paper, we utilize administrative panel data to examine the impact of weather shocks on violent and property crimes in Jamaica. We find strong evidence that a one-standard-deviation increase in the daily temperature (2○C) increases violent crime by 3.67 percent, due to an increase in the number of murders (3.44 percent), shootings (7.53 percent), and cases of aggravated assault (6 percent). However, our results suggest that temperature changes have no statistical impact on property crime. In addition, we find that a one-standard-deviation increase in rainfall (2 mm) reduces crimes such as shootings (1.53 percent), break-ins (2.27 percent), and larcenies (3.85 percent), but it has a minimal impact on other categories of crime.
Candesartan upregulates angiotensin‐converting enzyme 2 in kidneys of male animals by decreased ubiquitination
Authors: Wang Ping , Ren Zhiyun , Wang Weiwan , Liu Mingda , Jia Yutao , Zhang Mingzhuo , Xue Ying , Zhang Chenyang , Xu Jianteng , Wang Cheng , Wang Xiaoyan
Published: March 2024

Candesartan is a common angiotensin‐II receptor‐1 blocker used for patients with cardiovascular and renal diseases. Angiotensin‐converting enzyme 2 (ACE2) is a negative regulator of blood pressure (BP), and also a major receptor for coronaviruses. To determine whether and how candesartan upregulates ACE2, we examined BP and ACE2 in multi‐organs from male and female C57BL/6J mice treated with candesartan (1 mg/kg, i.p.) for 7 days. Relative to the vehicle, candesartan lowered BP more in males than females; ACE2 protein abundances were increased in kidneys, not lungs, hearts, aorta, liver, spleen, brain, or serum, only from males. Ace2‐mRNA was similar in kidneys. Candesartan also decreased BP in normal, hypertensive, and nephrotic male rats. The renal ACE2 was increased by the drug in normal and nephrotic male rats but not spontaneously hypertensive ones. In male mouse kidneys, ACE2 was distributed at sodium‐hydrogen‐exchanger‐3 positive proximal‐convoluted‐tubules; ACE2‐ubiquitination was decreased by candesartan, accompanied with increased ubiquitin‐specific‐protease‐48 (USP48). In candesartan‐treated mouse renal proximal‐convoluted‐tubule cells, ACE2 abundances and activities were increased while ACE2‐ubiquitination and colocalization with lysosomal and proteosomal markers were decreased. The silence of USP48 by siRNA caused a reduction of ACE2 in the cells. Thus, the sex‐differential ACE2 upregulation by candesartan in kidney from males may be due to the decreased ACE2‐ubiquitination, associated with USP48, and consequent degradation in lysosomes and proteosomes. This is a novel mechanism and may shed light on candesartan‐like‐drug choice in men and women prone to coronavirus infections.
E-cigarettes and Youth: The Known, the Unknown, and Implications for Stakeholders
Authors: Yammine Luba , Tovar Maria , Yammine Nastassia Anna , Becker Cabrina , Weaver Michael F.
Published: March 2024

Despite the decline in the prevalence of e-cigarette use among youth during the coronavirus disease 2019 pandemic, more than 2.5 million of US high and middle schoolers are still using e-cigarettes. Furthermore, those who use e-cigarettes are starting at a younger age and are using them more intensely, reflecting, at least in part, a high addiction liability of modern e-cigarettes. Beyond addiction, accumulating evidence suggests that, in the short-term, e-cigarettes are associated with cardiovascular and pulmonary effects, whereas the long-term effects of e-cigarette use are yet to be established. The aim of this review is to synthesize current knowledge on e-cigarette use among youth, including established and potential risks and efforts to date to curb youth exposure to e-cigarettes. In addition, we provide recommendations for health care providers, researchers, and other stakeholders to address this significant public health issue.
Head-to-head comparison of PSMA PET/CT and mpMRI for detecting biochemical recurrence of prostate cancer: A systematic review and meta-analysis
Authors: Zhang Xinru , Ma Zhe
Published: March 2024

Objectives

This study aimed to evaluate the performance of prostate-specific membrane antigen positron emission tomography/computed tomography (PSMA PET/CT) in comparison to multiparametric magnetic resonance imaging (mpMRI) for detecting biochemical recurrence of prostate cancer (PCa).

Materials and methods

We conducted a comprehensive search for articles published in PubMed, Web of Science, Embase, and the Cochrane Library, spanning the inception of the database until October 26, 2022, which included head-to-head comparisons of PSMA PET/CT and mpMRI for assessing the biochemical recurrence of PCa.

Results

A total of 5 studies including 228 patients were analyzed. The overall positivity rates of PSMA PET/CT and mpMRI for detecting biochemical recurrence of PCa after final treatment were 0.68 (95% confidence interval [CI], 0.52–0.89) and 0.56 (95% CI, 0.36–0.88), respectively. The positivity rates of PSMA PET/CT and mpMRI for detecting local recurrence, lymph node metastasis, and bone metastases were 0.37 (95% CI, 0.30–0.47) and 0.38 (95% CI, 0.22–0.67), 0.44 (95% CI, 0.35–0.56) and 0.25 (95% CI, 0.17–0.35), and 0.19 (95% CI, 0.11–0.31) and 0.12 (95% CI, 0.05–0.25), respectively. Compared with mpMRI, PSMA PET/CT exhibited a higher positivity rate for detecting biochemical recurrence and lymph node metastases, and no significant difference in the positivity rate of local recurrence was observed between these 2 imaging modalities.

Conclusions

Compared with mpMRI, PSMA PET/CT appears to have a higher positivity rate for detecting biochemical recurrence of PCa. Although both imaging methods showed similar positivity rates of detecting local recurrence, PSMA PET/CT outperformed PSMA PET/CT in detecting lymph node involvement and overall recurrence.
Effects of preoperative and postoperative carbohydrate loading on gastrointestinal function and stress-induced inflammation after radical prostatectomy
Authors: Wang Ke , Xiao Jiaming , Wang Ying , Fan Bo , Dai Zhihong , Chang Cheng , Wen Lijie , Zhang Yue , Bao Jia , Wang Liang , Liu Zhiyu
Published: March 2024

Background:

Early postoperative oral clear liquid diet has been shown to enhance postoperative recovery. However, the standard strategy for this diet has not been established. The authors’ aim was to investigate the combined effect of preoperative and early postoperative carbohydrate loading on postoperative stress and gastrointestinal function of patients by standardizing the starting time, type, volume, and concentration of carbohydrate drinks.

Materials and methods:

Fifty-three patients undergoing radical prostatectomy were randomly assigned to two groups. Both groups received a carbohydrate loading of 400 ml (12.5%) overnight and 2 h before surgery. The intervention group (n=29) started a 400 ml (12.5%) carbohydrate loading 6 h after surgery and consumed it within 24 h, while the control group (n=32) drank water. The primary outcomes–postoperative fasting blood glucose, fasting insulin, C-reactive protein (CRP), interleukin-6 levels, and gastrointestinal function–were recorded. Secondary outcomes included subjective comfort assessment, the first postoperative intake of semi-fluid food time, and drainage volume.

Results:

Compared with the control group, the intervention group had lower CRP levels on postoperative day 1 (POD1)/POD2 and less drainage volume on POD1. The intervention group also experienced shorter times to the first postoperative flatus and the first consumption of semi-fluid foods; their 72-h postoperative protein intake was higher than that of the control group.

Conclusion:

The results suggest that combined preoperative and postoperative carbohydrate loading can alleviate stress-induced inflammation and promote the recovery of postoperative gastrointestinal function.
Therapeutic targeting at genome mutations of liver cancer by the insertion of HSV1 thymidine kinase through Cas9-mediated editing
Authors: Kader Muhamuda , Sun Wei , Ren Bao-Guo , Yu Yan-Ping , Tao Junyan , Foley Lesley M. , Liu Silvia , Monga Satdarshan P. , Luo Jian-Hua
Published: March 2024

Background:

Liver cancer is one of the most lethal malignancies for humans. The treatment options for advanced-stage liver cancer remain limited. A new treatment is urgently needed to reduce the mortality of the disease.

Methods:

In this report, we developed a technology for mutation site insertion of a suicide gene (herpes simplex virus type 1- thymidine kinase) based on type II CRISPR RNA-guided endonuclease Cas9-mediated genome editing to treat liver cancers.

Results:

We applied the strategy to 3 different mutations: S45P mutation of catenin beta 1, chromosome breakpoint of solute carrier family 45 member 2-alpha-methylacyl-CoA racemase gene fusion, and V235G mutation of SAFB-like transcription modulator. The results showed that the herpes simplex virus type 1-thymidine kinase insertion rate at the S45P mutation site of catenin beta 1 reached 77.8%, while the insertion rates at the breakpoint of solute carrier family 45 member 2 – alpha-methylacyl-CoA racemase gene fusion were 95.1%–98.7%, and the insertion at V235G of SAFB-like transcription modulator was 51.4%. When these targeting reagents were applied to treat mouse spontaneous liver cancer induced by catenin beta 1S45P or solute carrier family 45 member 2-alpha-methylacyl-CoA racemase, the mice experienced reduced tumor burden and increased survival rate. Similar results were also obtained for the xenografted liver cancer model: Significant reduction of tumor volume, reduction of metastasis rate, and improved survival were found in mice treated with the targeting reagent, in comparison with the control-treated groups.

Conclusions:

Our studies suggested that mutation targeting may hold promise as a versatile and effective approach to treating liver cancers.
The Nudging Effect of a Reminder Letter to Reduce Duplicated Medications
Authors: Cheng Shou-Hsia , Chung Kuo-Piao , Wang Ying-Chieh , Tsai Hsin-Yun
Published: March 2024

Background:

The increasing trend of multiple chronic conditions across the world has worsened the problem of medication duplication in health care systems without gatekeeping or referral requirement. Thus, to overcome this problem, a reminder letter has been developed in Taiwan to nudge patients to engage in medication management.

Objective:

To evaluate the effect of reminder letter on reducing duplicated medications.

Research Design:

A 2-arm randomized controlled trial design.

Subjects:

Patients with duplicated medications in the first quarter of 2019.

Measures:

The Taiwanese single-payer National Health Insurance Administration identified the eligible patients for this study. A postal reminder letter regarding medication duplication was mailed to the patients in the study group, and no information was provided to the comparison group. Generalized estimation equation models with a difference-in-differences analysis were used to estimate the effects of the reminder letters.

Results:

Each group included 11,000 patients. Those who had received the reminder letter were less likely to receive duplicated medications in the subsequent 2 quarters (postintervention 1: odds ratio [OR]=0.95, 95% CI=0.87–1.03; postintervention_2: OR=0.99, 95% CI=0.90–1.08) and had fewer days of duplicated medications (postintervention 1: β=–0.115, P=0.015; postintervention 2 (β=–0.091, P=0.089) than those who had not received the reminder letter, showing marginal but significant differences.

Conclusions:

A one-off reminder letter nudge could mildly decrease the occurrence of duplicated medications. Multiple nudges or nudges incorporating behavioral science insights may be further considered to improve medication safety in health systems without gatekeeping.