bluuebunny/crossref_metadata_2025 huggingface dataset:
Potential role of mitochondria and endoplasmic reticulum in the response elicited by D-aspartate in TM4 Sertoli cells
Authors: Falvo Sara , Grillo Giulia , Latino Debora , Chieffi Baccari Gabriella , Di Fiore Maria Maddalena , Venditti Massimo , Petito Giuseppe , Santillo Alessandra
Published: July 2024

D-Aspartic Acid (D-Asp) affects spermatogenesis by enhancing the biosynthesis of the sex steroid hormones acting either through the hypothalamus-pituitary–testis axis or directly on Leydig cells. Recently, in vitro studies have also demonstrated the direct effects of D-Asp on the proliferation and/or activity of germ cells. However, although D-Asp is present in Sertoli cells (SC), the specific role of the amino acid in these cells remains unknown. This study investigated the effects of D-Asp on the proliferation and activity of TM4 SC, focusing on the mitochondrial compartment and its association with the endoplasmic reticulum (ER). We found that D-Asp enhanced the proliferation and activity of TM4 cells as evidenced by the activation of ERK/Akt/PCNA pathway and the increase in the protein levels of the androgen receptor. Furthermore, D-Asp reduced both the oxidative stress and apoptotic process. An increase in mitochondrial functionality and dynamics, as well as a reduction in ER stress, were also found in D-Asp-treated TM4 cells. It is known that mitochondria are closely associated with ER to form the Mitochondrial-Associated Endoplasmic Reticulum Membranes (MAM), the site of calcium ions and lipid transfer from ER to the mitochondria, and vice versa. The data demonstrated that D-Asp induced stabilization of MAM in TM4 cells. In conclusion, this study is the first to demonstrate a direct effect of D-Asp on SC activity and to clarify the cellular/molecular mechanism underlying these effects, suggesting that D-Asp could stimulate spermatogenesis by improving the efficiency of SC.
Synthesis and In vitro evaluation of bichalcones as novel anti-toxoplasma agents
Authors: Mazzone Flaminia , Klischan Moritz K. T. , Greb Julian , Smits Sander H. J. , Pietruszka Jörg , Pfeffer Klaus
Published: July 2024

Toxoplasmosis is a zoonotic disease caused by Toxoplasma gondii, an apicomplexan parasite that infects approximately a third of the world’s human population. This disease can cause serious complications during pregnancy and can be fatal in immunocompromised hosts. The current treatment options for toxoplasmosis face several limitations. Thus, to address the urgent medical need for the discovery of novel anti-toxoplasma potential drug candidates, our research focused on exploring a series of monomeric and dimeric chalcones, polyphenolic molecules belonging to the class of flavonoids. Chalcones 1aa—1bg and axially chiral A-A′-connected bichalcones 2aa—2bg were evaluated in vitro against the proliferation of the parasite in a cell-based assay. A comparison of the efficacy demonstrated that, in several cases, bichalcones exhibited increased bioactivity compared to their corresponding monomeric counterparts. Among these compounds, a bichalcone with a phenyl substituent and a methyl moiety 2ab showed the most potent and selective inhibitory activity in the nanomolar range. Both enantiomers of this bichalcone were synthesized using an axially chiral biphenol building block. The biaryl bond was forged using Suzuki cross-coupling in water under micellar catalysis conditions. Separation of the atropisomers of this biphenol building block was conducted by chiral HPLC on a preparative scale. The biological evaluation of the enantiomers revealed that the (Ra)-enantiomer (Ra)-2ab is the eutomer. These studies suggest that bichalcones may be important drug candidates for further in vivo evaluations for the discovery of anti-toxoplasma drugs.
Molecular and phenotypic characterization of Streptococcus pneumoniae isolates in a Japanese tertiary care hospital
Authors: Nakao Takumi , Kosai Kosuke , Akamatsu Norihiko , Ota Kenji , Mitsumoto-Kaseida Fujiko , Hasegawa Hiroo , Izumikawa Koichi , Mukae Hiroshi , Yanagihara Katsunori
Published: July 2024

This study aimed to investigate the bacterial characteristics of pneumococcal isolates obtained from a tertiary care hospital in Japan. We analyzed the antimicrobial susceptibility, possession of macrolide resistance genes, pneumococcal serogroup/serotype, and sequence type (ST) of pneumococcal isolates from patients aged 15 years or older between 2011 and 2020 at Nagasaki University Hospital. Of the 73 isolates analyzed, 86.3% showed resistance to macrolides, and 28.8%, 46.6%, and 11.0% harbored mefA, ermB, and both, respectively. Of the isolates possessing ermB, 97.6% showed high levels of macrolide resistance [minimal inhibitory concentration (MIC) range, > 16 µg/mL]. Solithromycin (MIC range, 0.03–0.25 µg/mL), regardless of the presence of macrolide resistance genes, and lascufloxacin (MIC range, 0.06–0.5 µg/mL) showed potent in vitro activity against pneumococci. Serotype 19A was the most prevalent (six isolates), followed by serotypes 10A, 15A, and 15B/C (five isolates each). Four serotypes (11A, 19A, 22F, and 23B) and five STs (36, 99, 433, 558, and 3111) were significantly correlated with the presence of macrolide resistance genes. All four isolates with serotype 11A/ST99 and three isolates with serotype 19A/ST3111 harbored both mefA and ermB. No macrolide resistance genes were detected in either of the two isolates with serotype 22F/ST433, while all ten isolates with serogroup 15 (serotypes 15A and 15B/C, five isolates each) possessed ermB alone. Our study revealed the bacterial characteristics of the pneumococcal isolates obtained from our hospital. In vitro activity of solithromycin and lascufloxacin against these isolates was confirmed.
Technologies and main functionalities of the telemonitoring application reCOVeryaID
Authors: D'Auria Daniela , Bettini Fabio , Tognarelli Selene , Calvanese Diego , Menciassi Arianna
Published: July 2024

The COVID-19 pandemic has highlighted the need to take advantage of specific and effective patient telemonitoring platforms, with specific reference to the constant monitoring of vital parameters of patients most at risk. Among the various applications developed in Italy, certainly there is reCOVeryaID, a web application aimed at remotely monitoring patients potentially, currently or no longer infected with COVID-19. Therefore, in this paper we present a system model, consisting of a multi-platform intelligent telemonitoring application, that enables remote monitoring and provision of integrated home care to both patients symptomatic, asymptomatic and pre-symptomatic with severe acute respiratory infectious disease or syndrome caused by viruses belonging to the Coronavirus family, as well as simply to people with respiratory problems and/or related diseases (chronic obstructive pulmonary disease or asthma). In fact, in this paper we focus on exposing the technologies and various functionalities offered by the system, which constitute the practical implementation of the theoretical framework described in detail in another paper. Specifically, the reCOVeryaID telemonitoring application is a stand-alone, knowledge base-supported application that can promptly react and inform physicians if dangerous trends in a patient's short- and long-term vital signs are detected, thus enabling them to be monitored continuously, both in the hospital and at home. The paper also reports an evaluation of user satisfaction, carried out by actual patients and medical doctors.
Study on wind-sand dynamics observation of blowout in Xilingol sandy grassland
Authors: Gao Tianxiao , Gao Yong , Huang Luxi , Yang Juan , Yang Wenyuan , Guo Xiaoyu
Published: July 2024

This study investigated airflow changes and sediment transport in the blowouts of the sandy grassland in Xilingol, Inner Mongolia. The results show that the wind direction inside the blowout is influenced by the direction of the incoming wind. Specifically, when the angle between the incoming wind direction and the long axis of the blowout is less than 15°, both sides of the wall tend to generate a wind flow towards the east exit. Meanwhile, the main airflow along the central axis airflow deflects towards the north side wall. However, when the angle is greater than 15°, the airflow on the north wall first disperses and then converges towards the wellbore. Conversely, the airflow on the south wall blows out in a southeast direction, and the axial airflow deflects towards the south wall. The rate of wind speed acceleration on both sides of the wall increases with height within the blowout but decreases along the central axis section. Higher wind speeds correlate with greater cumulative sand transport heights. Sand transport heights on both sides of the deflation basin are smaller than those along the central axis section, with the opposite observed in the depositional lobe. The rate of sand transport is primarily influenced by wind direction and wind speed, followed by, topography, vegetation coverage, slope, and aspect. These variations in airflow, combined with sediment transport, lead to the blowout taking on a develop deeper, longer, and wider shape.
Effects of exercise training on growth and physiology of large-mouth bass (Micropterus salmoides) reared in a recirculating aquaculture system
Authors: Ji Mingdong , Li Haijun
Published: July 2024

Large-mouth bass originally lived in rivers and lakes and now is often raised in recirculating aquaculture systems (RAS). However, the shortcoming of RAS is that there is very limited space for swimming fish in a high-density culture environment, thus leading to a lack of exercise. To investigate the effects of exercise training on growth performance, digestive enzymes, stress, and antioxidant capacity of large-mouth bass in a RAS, three training water flow velocities with three replicates were used in the present study: low water velocity: 0.5 body length per second (bl/s) (LV); medium water velocity: 1 bl/s (MV); and high water velocity: 1.5 bl/s (HV). 270 large-mouth bass (average initial body weight 47.51 ± 1.44 g, initial body length 12.71 ± 0.06 cm) were randomly divided into nine tanks (30 fish per tank). After 27 days experiment, the results showed that the growth performance of large-mouth bass, including feed intake, weight gain rate, and specific growth rate, in the HV group was significantly higher compared to the other groups. On the physiological level, the lipase and amylase activities were significantly increased in the HV group compared to the other groups. For the stress response parameters, the cortisol, glucose and lactate concentrations in the HV group were significantly increased, which may indicate higher stress in the HV group. Regarding the antioxidant enzyme activities, the activities of catalase (CAT) and glutathione peroxidase (GSH-PX) in the LV group were significantly higher than those in the HV group, which indicated that fish suffered higher oxidative stress in the LV group. Regarding the immune-related parameters, LZM and ACP activities had no significant differences among the groups, while AKP activities in the MV and HV groups were significantly higher than that in the LV group. Overall, the results demonstrated that exercise training had significant effects on the growth, digestion, stress, and immune response of large-mouth bass. It is suggested that exercise training with 1.5 bl/s can enhance fish growth, however, it also presents a potential risk of inducing stress in fish. Therefore, in rearing large-mouth bass in RAS, the setting of water flow velocity should not only focus on the growth of large-mouth bass but also consider its welfare.
UV-absorbing mycosporine-like amino acids in the eyes of temperate marine and freshwater fish species
Authors: Bonin Jane , Hammerle Fabian J. , Ganzera Markus , Krumme Uwe , Karsten Ulf
Published: July 2024

Ultraviolet radiation (UVR) is the photochemically most reactive waveband of incident solar irradiation. Despite high absorption in aquatic environments, UVR causes numerous biochemical, genetic, and cytotoxic effects in aquatic organisms. To counteract UVR stress, many of those species are able to synthesize, accumulate, or acquire UV-sunscreen compounds for photoprotection from their diet. The most abundant UV sunscreens in marine and freshwater organisms are mycosporine-like amino acids (MAAs), which exhibit high molar extinction coefficients in the UVR range along with a strong photo- and heat stability. In this study, we investigated the qualitative and quantitative MAA distribution patterns in the eyes of 39 fish species, mainly from the temperate northern hemisphere (Baltic Sea, Northern Atlantic), using state-of-the-art analytical methods. The fish eyes of the most investigated species (33 taxa) contained MAAs, between one and seven different compounds. The MAAs palythine, asterina-330, palythene, and usujirene were present (as previously reported), and three new compounds, aplysiapalythine A, porphyra-334, and shinorine, were identified. Total MAA concentrations covered a wide range from trace amounts to > 4.2 mg g−1 dry weight, thereby providing the first quantitative data on MAAs in fish eyes. The highest MAA contents were measured in Sprattus sprattus, which are comparable to those of intertidal red seaweeds. The trophic transfer of MAAs from primary producers via zooplankton to the fish is discussed, along with the localization in the fish eye as well as possible additional functions.
Isolation and identification of a novel porcine-related recombinant mammalian orthoreovirus type 3 strain from cattle in Guangxi Province, China
Authors: Luo Yuhang , Wang Yanglin , Tang Wenfei , Wang Cui , Liu Huanghao , Wang Xiaoling , Xie Jiang , Wang Jie , Ouyang Kang , Chen Ying , Wei Zuzhang , Qin Yifeng , Pan Yan , Huang Weijian
Published: July 2024

The Mammalian orthoreovirus (MRV) infects various mammals, including humans, and is linked to gastrointestinal, respiratory, and neurological diseases. A recent outbreak in Liuzhou, Guangxi, China, led to the isolation of a new MRV strain, GXLZ2301, from fecal samples. This strain replicates in multiple cell lines and forms lattice-like structures. Infected cells exhibit single-cell death and syncytia formation. The virus’s titers peaked at 107.2 TCID50/0.1 mL in PK-15 and BHK cells, with the lowest at 103.88 TCID50/0.1 mL in A549 cells. Electron microscopy showed no envelope with a diameter of about 70 nm. Genetic analysis revealed GXLZ2301 as a recombinant strain with gene segments from humans, cows, and pigs, similar to type 3 MRV strains from Italy (2015-2016). Pathogenicity tests indicated that while the bovine MRV strain did not cause clinical symptoms in mice, it caused significant damage to the gut, lungs, liver, kidneys, and brain. The emergence of this MRV strain may pose a threat to the health of animals and humans, and it is recommended that its epidemiology and recombination be closely monitored.
Schisandra chinensis inhibits the entry of BoHV-1 by blocking PI3K-Akt pathway and enhances the m6A methylation of gD to inhibit the entry of progeny virus
Authors: Liu Yang , Wang Kang , Gong Xiao , Qu Weijie , Xiao Yangyang , Sun Hongtao , Kang Jingli , Sheng Jinliang , Wu Faxing , Dai Feiyan
Published: July 2024

Schisandra chinensis, a traditional Chinese medicine known for its antitussive and sedative effects, has shown promise in preventing various viral infections. Bovine herpesvirus-1 (BoHV-1) is an enveloped DNA virus that causes respiratory disease in cattle, leading to significant economic losses in the industry. Because the lack of previous reports on Schisandra chinensis resisting BoHV-1 infection, this study aimed to investigate the specific mechanisms involved. Results from TCID50, qPCR, IFA, and western blot analyses demonstrated that Schisandra chinensis could inhibit BoHV-1 entry into MDBK cells, primarily through its extract Methylgomisin O (Meth O). The specific mechanism involved Meth O blocking BoHV-1 entry into cells via clathrin- and caveolin-mediated endocytosis by suppressing the activation of PI3K-Akt signaling pathway. Additionally, findings from TCID50, qPCR, co-immunoprecipitation and western blot assays revealed that Schisandra chinensis blocked BoHV-1 gD transcription through enhancing m6A methylation of gD after virus entry, thereby hindering gD protein expression and preventing progeny virus entry into cells and ultimately inhibiting BoHV-1 replication. Overall, these results suggest that Schisandra chinensis can resist BoHV-1 infection by targeting the PI3K-Akt signaling pathway and inhibiting gD transcription.
Unraveling the molecular landscape of lead-induced cochlear synaptopathy: a quantitative proteomics analysis
Authors: Bhatia Pankaj , Mehmood Shomaila , Doyon-Reale Nicole , Rosati Rita , Stemmer Paul M. , Jamesdaniel Samson
Published: July 2024

Introduction

Exposure to heavy metal lead can cause serious health effects such as developmental neurotoxicity in infants, cognitive impairment in children, and cardiovascular and nephrotoxic effects in adults. Hearing loss is one of the toxic effects induced by exposure to lead. Previous studies demonstrated that exposure to lead causes oxidative stress in the cochlea and disrupts ribbon synapses in the inner hair cells.

Methods

This study investigated the underlying mechanism by evaluating the changes in the abundance of cochlear synaptosomal proteins that accompany lead-induced cochlear synaptopathy and hearing loss in mice. Young-adult CBA/J mice were given lead acetate in drinking water for 28 days.

Results

Lead exposure significantly increased the hearing thresholds, particularly at the higher frequencies in both male and female mice, but it did not affect the activity of outer hair cells or induce hair cell loss. However, lead exposure decreased wave-I amplitude, suggesting lead-induced cochlear synaptopathy. In agreement, colocalization of pre- and post-synaptic markers indicated that lead exposure decreased the number of paired synapses in the basal turn of the cochlea. Proteomics analysis indicated that lead exposure increased the abundance of 352 synaptic proteins and decreased the abundance of 394 synaptic proteins in the cochlea. Bioinformatics analysis indicated that proteins that change in abundance are highly enriched in the synaptic vesicle cycle pathway.

Discussion

Together, these results suggest that outer hair cells are not the primary target in lead-induced ototoxicity, that lead-induced cochlear synaptopathy is more pronounced in the basal turn of the cochlea, and that synaptic vesicle cycle signaling potentially plays a critical role in lead-induced cochlear synaptopathy.
Long-term efficacy, safety, and patient-reported outcomes of apitegromab in patients with spinal muscular atrophy: results from the 36-month TOPAZ study
Authors: Crawford Thomas O. , Day John W. , De Vivo Darryl C. , Krueger Jena M. , Mercuri Eugenio , Nascimento Andres , Pasternak Amy , Mazzone Elena Stacy , Duong Tina , Song Guochen , Marantz Jing L. , Baver Scott , Yu Dongzi , Liu Lan , Darras Basil T.
Published: July 2024

Background and purpose

At 12 months in the phase 2 TOPAZ study, treatment with apitegromab was associated with both an improved motor function in patients with Type 2 or 3 spinal muscular atrophy (SMA) and with a favorable safety profile. This manuscript reports the extended efficacy and safety in the nonambulatory group of the TOPAZ study at 36 months.

Methods

Patients who completed the primary study (NCT03921528) could enroll in an open-label extension, during which patients received apitegromab 20 mg/kg by intravenous infusion every 4 weeks. Patients were assessed periodically via the Hammersmith Functional Motor Scale–Expanded (HFMSE), Revised Upper Limb Module (RULM), World Health Organization (WHO) motor development milestones, Pediatric Evaluation of Disability Inventory Computer Adaptive Test (PEDI-CAT) Daily Activities and Mobility domains, and Patient-Reported Outcomes Measurement Information System (PROMIS) Fatigue questionnaire.

Results

Of the 58 patients enrolled in TOPAZ, 35 were nonambulatory (mean age 7.3 years). The mean change at 36 months in HFMSE score from baseline was +4.0 (standard deviation [SD]: 7.54), and + 2.4 (3.24) for RULM score (excluding n = 7 after scoliosis surgery). Caregiver-reported outcomes (PEDI-CAT and PROMIS Fatigue) showed improvements from baseline over 36 months. In addition, most patients (28/32) improved or maintained WHO motor milestones achieved at baseline. The most frequently reported treatment-emergent adverse events were pyrexia (48.6%), nasopharyngitis (45.7%), COVID-19 infection (40.0%), vomiting (40.0%), and upper respiratory tract infection (31.4%).

Conclusion

The benefit of apitegromab treatment observed at 12 months was sustained at 36 months with no new safety findings.
Performance of simplified methods for quantification of [18F]NaF uptake in fibrodysplasia ossificans progressiva
Authors: de Ruiter Ruben Daniel , Botman Esmée , Teunissen Bernd P. , Lammertsma Adriaan Anthonius , Boellaard Ronald , Raijmakers Pieter G. , Schwarte Lothar A. , Nieuwenhuijzen Jakko A. , Gonzalez Trotter Dinko , Eekhoff Elisabeth Marelise W. , Yaqub Maqsood
Published: July 2024

Background

Fibrodysplasia Ossificans Progressiva (FOP) is a rare, genetic disease in which heterotopic bone is formed in muscles, tendons and ligaments throughout the body. Disease progression is variable over time and between individuals. 18F-fluoride uptake in newly formed bone can be evaluated using [18F]NaF (i.e., sodiumfluoride) PET/CT, identifying active areas of bone formation in FOP. The purpose of this study was to assess the performance of various semi-quantitative methods with full kinetic analysis.

Results

Seven patients (age range: 20–31 years) with FOP underwent dynamic [18F]NaF scans at baseline and after one year. [18F]NaF uptake was measured in aorta descendens, vertebrae, heterotopic bone lesions and metabolically active regions on PET, and quantified using nonlinear regression (NLR) analysis together with standardized uptake value (SUV) and target-to-blood ratio (TBR). SUV was on measured the 40–45 min frame of the dynamic sequence (SUV40–45) and on the subsequent static sweep (SUVStatic). Correlations between and SUV40–45 and NLR-derived Ki were comparable when normalized to body weight (r = 0.81, 95% CI 0.64–0.90), lean body mass (r = 0.79, 95% CI 0.61–0.89) and body surface area (r = 0.84, 95% CI 0.70–0.92). Correlation between TBR40–45 and NLR-derived Ki (r = 0.92, 95% CI 0.85–0.96) was higher than for SUV40–45. Correlation between TBR40–45 and NLR-derived Ki was similar at baseline and after one year (r = 0.93 and 0.94). The change in TBR40–45 between baseline measurement and after one year correlated best with the change in NLR-derived Ki in the PET-active lesions (r = 0.87).

Conclusion

The present data supports the use of TBR for assessing fluoride uptake in PET-active lesions in FOP.

Clinical trial registration

Sub-study of the Lumina-1 trial (clinicaltrials.gov, NCT03188666, registered 13-06-2017).
Association between composite dietary antioxidant index and metabolic dysfunction associated steatotic liver disease: result from NHANES, 2017-2020
Authors: Zhang Zhaofu , Wang Hao , Chen Youpeng
Published: July 2024

Background

The development of metabolic dysfunction associated steatotic liver disease (MASLD) has been associated with lipid accumulation, oxidative stress, endoplasmic reticulum stress, and lipotoxicity. The Composite Dietary Antioxidant Index (CDAI) is a comprehensive score representing an individual intake of various dietary antioxidants, including vitamin A, vitamin C, vitamin E, selenium, zinc, and carotenoids. This study investigated the association between CDAI and MASLD.

Materials and methods

Clinical and demographic data, as well as ultrasound transient elastography measurements at baseline, were collected from the National Health and Nutrition Examination Survey 2017–2020 (NHANES 2017–2020). The controlled attenuation parameter was utilized to diagnose the presence of hepatic steatosis and to categorize individuals into those with and without MASLD. Liver stiffness was measured by ultrasound transient elastography, and subjects were classified as those with and without advanced liver fibrosis.

Results

This study included 5,884 adults, of whom 3,433 were diagnosed with MASLD, resulting in a weighted prevalence of 57.3%. After adjusting for covariates, the odds ratios for MASLD were 0.96 (95% CI: 0.82, 1.12) in the second quartile, 0.80 (95% CI: 0.68, 0.95) in the third quartile and 0.60 (95% CI: 0.49, 0.73) in the fourth quartile, respectively. CDAI, however, was not significantly associated with advanced liver fibrosis.

Conclusion

These findings suggested that scores on the CDAI were linearly and negatively associated with the prevalence of MASLD in the United States adults.
Oculometric biomarkers of visuomotor deficits in clinically asymptomatic patients with systemic lupus erythematosus undergoing long-term hydroxychloroquine treatment
Authors: Berneshawi Andrew R. , Seyedmadani Kimia , Goel Rahul , Anderson Mark R. , Tyson Terence L. , Akay Yasmin M. , Akay Metin , Leung Loh-Shan B. , Stone Leland S.
Published: July 2024

Introduction

This study examines a set of oculomotor measurements, or “oculometric” biomarkers, as potential early indicators of visual and visuomotor deficits due to retinal toxicity in asymptomatic Systemic Lupus Erythematosus (SLE) patients on long-term hydroxychloroquine (HCQ) treatment. The aim is to identify subclinical functional impairments that are otherwise undetectable by standard clinical tests and to link them to structural retinal changes.

Methods

We measured oculomotor responses in a cohort of SLE patients on chronic HCQ therapy using a previously established behavioral task and analysis technique. We also examined the relationship between oculometrics, OCT measures of retinal thickness, and standard clinical perimetry measures of visual function in our patient group using Bivariate Pearson Correlation and a Linear Mixed-Effects Model (LMM).

Results

Significant visual and visuomotor deficits were found in 12 asymptomatic SLE patients on long-term HCQ therapy compared to a cohort of 17 age-matched healthy controls. Notably, six oculometrics were significantly different. The median initial pursuit acceleration was 22%, steady-state pursuit gain 16%, proportion smooth 7%, and target speed responsiveness 31% lower, while catch-up saccade amplitude was 46% and fixation error 46% larger. Excluding the two patients with diagnosed mild toxicity, four oculometrics, all but fixation error and proportion smooth, remained significantly impaired compared to controls. Across our population of 12 patients (24 retinae), we found that pursuit latency, initial acceleration, steady-state gain, and fixation error were linearly related to retinal thickness even when age was accounted for, while standard measures of clinical function (Mean Deviation and Pattern Standard Deviation) were not.

Discussion

Our data show that specific oculometrics are sensitive early biomarkers of functional deficits in SLE patients on HCQ that could be harnessed to assist in the early detection of HCQ-induced retinal toxicity and other visual pathologies, potentially providing early diagnostic value beyond standard visual field and OCT evaluations.
Open surgical excision vs. endoscopic radiofrequency ablation in managing congenital pyriform sinus fistula—a comprehensive analysis of 166 cases
Authors: Xu Mengrou , Chen Wei , Chen Jiarui , Li Xiaoyan
Published: July 2024

Background

Congenital pyriform sinus fistula (CPSF) is uncommon congenital abnormality, and the optimal definitive treatment has not yet been established. The aim of the present study was to comparatively evaluate patients with CPSF regarding the indications and outcomes of treatment with open surgical excision (OSE) vs. endoscopic Radiofrequency Ablation (RA), and the advantages of both therapeutic procedures were also analyzed.

Methods

An observational, longitudinal, retrospective, analytical and comparative study was conducted on 166 consecutive pediatric patients with CPSF treated at Shanghai Children's Hospital between December 2018 and September 2023.

Results

In this study, there were 79 males and 87 females. The median age at operation was 4.8 years (8 days to 15 years). OSE and Endoscopic RA were respectively performed in 48 and 118 children. The gastric tube retention time after RA was longer (3 days vs. 14 days) than after OSE. Patients with a history of incision and drainage (I&D) tended to choose OSE (75.0% vs. 39.0%, P < 0.01). There were no significant differences in postoperative complications and recurrence rates between these two groups (P > 0.05), but the hospitalization duration was shorter for RA group compared to OSE group [2 (2–3) vs. 4 (3–5), P < 0.01].

Conclusions

Both OSE and RA are recognized as first-line treatment options for CPSF, which show no significant differences in prognosis, except hospitalization duration and the gastric tube retention time. Nevertheless, the indications for OSE and RA differ, which are influenced by factors such as the inflammatory stage, specific typing, previous treatments, and the surgeon's expertise. The selection of surgical approach should be carefully determined based on individual circumstances.
Association between PER and CRY gene polymorphisms and the response to caffeine citrate treatment in infants with apnea of prematurity
Authors: Xie Jiang-Biao , Zhuang Wei , Zhu Yao , Zheng Zhi , Huang Yan-Ru , Ma Si-Min , Lin Xin-Zhu
Published: July 2024

Background

Circadian rhythms impact metabolism and the therapeutic effects of drugs. The purpose of this study was to determine the association between PER and CRY polymorphisms and caffeine citrate treatment response in infants with apnea of prematurity.

Methods

A total of 221 preterm infants of gestational age <34 weeks were included in this study (160 in the response group and 61 in the non-response group). The propensity score matching method was used to perform a 1:1 matching for all premature infants, and the general characteristics and clinical outcomes of the two groups were compared. The association between polymorphisms of the circadian transcription repressors PER and CRY and caffeine citrate treatment response in infants with apnea of prematurity was analyzed with co-dominant, dominant, recessive, and over-dominant models, as well as analysis of alleles. Generalized multifactor dimensionality reduction (GMDR) analysis was used to analyze the interaction between the PER and CRY genes.

Results

After propensity score matching, 45 preterm infants were included in each of the response and non-response groups, and there were no statistically significant differences in general characteristics between the two groups (P > 0.05). Infants in the non-response groups had a higher incidence of moderate and severe bronchopulmonary dysplasia (BPD) (P = 0.043), retinopathy of prematurity (ROP) (P = 0.035), and invasive ventilation (P = 0.027), and their duration of oxygen use (P = 0.041) was longer. When corrected for false discovery rate, the PER3 rs228669 recessive model (PFDR = 0.045) and the over-dominant model (PFDR = 0.045) were both associated with caffeine citrate treatment response. Preterm infants with the rs228669 CC genotype had a significantly lower rate of caffeine citrate non-response in the recessive model (OR = 0.28, 95% CI = 0.12–0.66), which was significantly higher in preterm infants with the CT genotype in the over-dominant model (OR = 4.18, 95% CI = 1.64–10.66). GMDR analysis revealed an interaction between the PER and CRY genes (P < 0.05).

Conclusions

Circadian rhythms may play a role in the response of premature infants to caffeine citrate, and polymorphisms of the PER and CRY genes may influence the effectiveness of caffeine citrate treatment for apnea of prematurity.
A new crystalline daidzein-piperazine salt with enhanced solubility, permeability, and bioavailability
Authors: Meng Jiacheng , Qiu Chenxu , Lu Chenyue , He Xin , Zhao Xinghua
Published: July 2024

To overcome the poor solubility, permeability, and bioavailability of the plant isoflavone daidzein (DAI), a novel salt of DAI with anhydrous piperazine (PIP) was obtained based on cocrystallization strategy. The new salt DAI-PIP was characterized by powder X-ray diffraction (PXRD), differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), Fourier-transform infrared (FT-IR) spectroscopy, and optical microscopy. The results showed that the maximum apparent solubility (Smax) of DAI-PIP increased by 7.27-fold and 1000-fold compared to DAI in pH 6.8 buffer and water, respectively. The peak apparent permeability coefficient (Papp) of DAI-PIP in the Caco-2 cell model was 30.57 ± 1.08 × 10−6 cm/s, which was 34.08% higher than that of DAI. Additionally, compared to DAI, the maximum plasma concentration (Cmax) value of DAI-PIP in beagle dogs was approximately 4.3 times higher, and the area under the concentration-time curve (AUC0-24) was approximately 2.4 times higher. This study provides a new strategy to enhance the dissolution performance and bioavailability of flavonoid drugs, laying a foundation for expanding their clinical applications.
Wnt/β-catenin pathway as a potential target for Parkinson’s disease: a cohort study of romosozumab using routinely collected health data in Japan
Authors: Inokuchi Shoichiro , Shimamoto Koji
Published: July 2024

Introduction

Romosozumab is a monoclonal antibody approved for osteoporosis which targets sclerostin, an endogenous inhibitor of Wnt/β-catenin pathway. Given the essential roles of the Wnt/β-catenin pathway in various tissues, we hypothesized romosozumab treatment may influence other conditions.

Methods

This cohort study included patients prescribed romosozumab or parathyroid receptor (PTHR) agonists after 1 January 2019, using a Japanese electronic medical record database. The outcomes of interest included autoimmune disease, interstitial pneumonia, cardiovascular outcome, Alzheimer’s disease, Parkinson’s disease (PD), serious infections, and malignancies. A stabilized inverse probability-weighted Cox proportional hazard model was used to estimate the hazard ratios. Age- and gender-based subgroup analyses were conducted. Exploratory outcomes based on three-digit International Classification of Diseases 10th Revision-based were also examined.

Results

In total, 2,673 patients treated with romosozumab and 5,980 treated with PTHR agonists were identified, respectively. While most outcomes of interest showed no association with romosozumab, the risk of PD decreased with romosozumab (hazard ratio [95% confidence interval], 0.37 [0.14–0.94]) compared with PTHR agonist. Regarding the cardiovascular outcome, no notable association was identified overall; however, gender-based subgroup analysis suggested that male sex may be a potential risk factor with romosozumab treatment. Only 16 of 903 exploratory outcomes were potentially influenced by romosozumab.

Conclusion

Romosozumab lowered the risk of PD development compared with PTHR agonist. The study also highlights the utility of routinely collected health data for drug repositioning. While further validation is warranted, the findings suggest that the Wnt-β-catenin pathway holds promise as a therapeutic target for PD.
Plant-parasitic nematode research in the arid desert landscape: a systematic review of challenges and bridging interventions
Authors: Elhady Ahmed , Alghanmi Linah , Abd-Elgawad Mahfouz M. M. , Heuer Holger , Saad Maged M. , Hirt Heribert
Published: July 2024

Plant-parasitic nematode research in the Middle East and North Africa (MENA) region faces significant challenges rooted in a need for proper assembly, diversity, and a unified and purpose-driven framework. This led to exacerbating their detrimental effects on crop production. This systematic review addresses the current situation and challenges that require targeted interventions to sustainably manage plant-parasitic nematodes and reduce their detrimental impact on agriculture production in the MENA region. We analyzed the nematode-related research conducted within the region over the past three decades to assess available resources and promote diverse research approaches beyond basic morphology-focused surveys. We show that crops are attacked by a diverse spectrum of plant-parasitic nematodes that exceed the global economic threshold limits. In particular, Meloidogyne species exceed the threshold limit by 8 - 14-fold, with a 100% frequency of occurrence in the collected soil samples, posing a catastrophic threat to crop production and the economy. We highlight detrimental agriculture practices in the MENA region, such as transferring soil from established fields to barren land, which enhances the dissemination of plant-parasitic nematodes, disrupting soil ecology and causing significant agricultural challenges in newly cultivated areas. Looking into the behavior of farmers, raising awareness must be accompanied by available solutions, as more practical alternatives are needed to gain the confidence of the farmers. We propose integrating microbial-based products and soil development practices in hygienic farming as resilient and sustainable solutions for nematode management. Increased emphasis is required to diversify the nematode-related research areas to bridge the gaps and facilitate the transition from fundamental knowledge to practical solutions. A cohesive network of nematologists and collaboration with national and international entities is crucial for exchanging knowledge related to legislation against invasive species.
Exploring the effect of environmental sensitivity on emotional fluctuations among adolescents during the COVID-19 pandemic: a three-wave longitudinal study
Authors: Dragone Mirella , Colella Alessandra , Esposito Concetta , Bacchini Dario
Published: July 2024

Introduction

The COVID-19 pandemic significantly impacted the emotional well-being of adolescents worldwide. Some studies suggested that individuals with high Environmental Sensitivity may have been more likely to experience poor psychological adjustment during the pandemic than those with lower sensitivity. However, there is still limited research on how emotional responses varied across different stages of the pandemic and whether Environmental Sensitivity increased adolescents’ vulnerability to the psychological impact of prolonged pandemic restrictions.

Methods

To address this gap, this study used a three-year longitudinal design (2020–2022) with a sample of 453 adolescents. They completed an online survey measuring their positive and negative emotions throughout the pandemic period, with Environmental Sensitivity considered a time-invariant covariate.

Results

The results revealed that all participants, regardless of their level of Environmental Sensitivity, experienced a decrease in positive emotionality between the first and second years. However, this trend reversed, showing an increase between the second and third years. Regarding negative emotions, highly sensitive adolescents experienced a significant linear increase over time. In contrast, low-and medium-sensitive adolescents exhibited a quadratic trend, with a notable increase in negative emotions between the first and second years, followed by a slight decrease between the second and third years.

Discussion

These findings provide further evidence of the negative impact of the pandemic on adolescents’ emotional well-being. They also support the notion that Environmental Sensitivity is associated with individuals’ ability to respond and adjust to adverse life events, with significant implications for future research and practice.
Towards reconciling usability and usefulness of policy explanations for sequential decision-making systems
Authors: Tambwekar Pradyumna , Gombolay Matthew
Published: July 2024

Safefy-critical domains often employ autonomous agents which follow a sequential decision-making setup, whereby the agent follows a policy to dictate the appropriate action at each step. AI-practitioners often employ reinforcement learning algorithms to allow an agent to find the best policy. However, sequential systems often lack clear and immediate signs of wrong actions, with consequences visible only in hindsight, making it difficult to humans to understand system failure. In reinforcement learning, this is referred to as the credit assignment problem. To effectively collaborate with an autonomous system, particularly in a safety-critical setting, explanations should enable a user to better understand the policy of the agent and predict system behavior so that users are cognizant of potential failures and these failures can be diagnosed and mitigated. However, humans are diverse and have innate biases or preferences which may enhance or impair the utility of a policy explanation of a sequential agent. Therefore, in this paper, we designed and conducted human-subjects experiment to identify the factors which influence the perceived usability with the objective usefulness of policy explanations for reinforcement learning agents in a sequential setting. Our study had two factors: the modality of policy explanation shown to the user (Tree, Text, Modified Text, and Programs) and the “first impression” of the agent, i.e., whether the user saw the agent succeed or fail in the introductory calibration video. Our findings characterize a preference-performance tradeoff wherein participants perceived language-based policy explanations to be significantly more useable; however, participants were better able to objectively predict the agent’s behavior when provided an explanation in the form of a decision tree. Our results demonstrate that user-specific factors, such as computer science experience (p < 0.05), and situational factors, such as watching agent crash (p < 0.05), can significantly impact the perception and usefulness of the explanation. This research provides key insights to alleviate prevalent issues regarding innapropriate compliance and reliance, which are exponentially more detrimental in safety-critical settings, providing a path forward for XAI developers for future work on policy-explanations.
Co-teaching in higher education: implications for teaching, learning, engagement, and satisfaction
Authors: Zach Sima , Avugos Simcha
Published: July 2024

Introduction

This study examined the impact of co-teaching on students and lecturers, assessing its benefits and drawbacks, and suggesting ways to enhance collaborative learning.

Methods

Fifty undergraduate student teachers participated in two sports sciences seminar courses jointly taught by two lecturers. Data was collected via student reflections; course evaluation feedback; word clouds; and teacher reflections. Thematic analysis was used for qualitative data.

Results

The findings indicate that the short intensive seminar course resulted in three parallel processes: emotional, students transitioning from negative feelings of chaos, frustration, and a sense of incompetence to positive feelings of satisfaction and sense of accomplishment; social, students learning to listen, request assistance, support, encourage, and collaborate; and cognitive, students learning to ask fruitful questions, plan experiments, summarize, and present. Nevertheless, the time and effort demands involved in the planning and management of such courses may constitute a significant barrier to the future implementation of this teaching method. In terms of course outcomes, no indications of higher quality were seen compared to traditional instruction.

Discussion

Drawing on the symbolic interactionism theory, the study advocates for preparing students for inclusive and collaborative learning environments to improve academic engagement and success.
County-level total factor productivity of food in China and its spatio-temporal evolution and drivers
Authors: Liu Yang , Jiang Hui , Cui JunFu
Published: July 2024

In the context of the ongoing process of high-quality development in the new era, which is focused on improving total factor productivity, it is of great importance to explore the spatial and temporal variations of total factor productivity growth and its driving factors in China’s county regions’ grain cultivation industry. This paper employs a three-stage DEA-Malmquist productivity method, the Gini coefficient method, and a panel fixed-effects model to analyze data from Chinese counties between 2009 and 2019. The analysis indicates that the growth of county food total factor productivity (FTFP) exhibits a fluctuating upward trend during the examination period, with an average annual growth rate of 2.43%. This is primarily driven by technological progress, yet the core driving role of technological efficiency is not effectively played. The average annual growth rate of county FTFP varies across different regions. The highest average annual growth rate of county FTFP in the eastern region and the primary grain-producing area is 2.75 and 3.04%, respectively. The lowest growth rates were observed in the western region and the main grain marketing area, at 1.44 and 1.23%, respectively. Secondly, the Gini coefficient of county FTFP continues to demonstrate a persistent upward trend during the examination period, with an average annual growth rate of 14.729%. The primary factor contributing to the observed variation in total factor productivity growth of the food sector at the regional level is the existence of disparate technological progress. Thirdly, there is a notable positive correlation between county financial deepening and financial self-sufficiency rates and county FTFP growth, with impact coefficients of 0.0503 and 0.0924, respectively. Conversely, county population density, degree of economic development, farmers’ income level, and industrial structure exert a significant negative influence on county FTFP growth and technological progress.
Transforming environmental health datasets from the comparative toxicogenomics database into chord diagrams to visualize molecular mechanisms
Authors: Wyatt Brent , Davis Allan Peter , Wiegers Thomas C. , Wiegers Jolene , Abrar Sakib , Sciaky Daniela , Barkalow Fern , Strong Melissa , Mattingly Carolyn J.
Published: July 2024

In environmental health, the specific molecular mechanisms connecting a chemical exposure to an adverse endpoint are often unknown, reflecting knowledge gaps. At the public Comparative Toxicogenomics Database (CTD; https://ctdbase.org/), we integrate manually curated, literature-based interactions from CTD to compute four-unit blocks of information organized as a potential step-wise molecular mechanism, known as “CGPD-tetramers,” wherein a chemical interacts with a gene product to trigger a phenotype which can be linked to a disease. These computationally derived datasets can be used to fill the gaps and offer testable mechanistic information. Users can generate CGPD-tetramers for any combination of chemical, gene, phenotype, and/or disease of interest at CTD; however, such queries typically result in the generation of thousands of CGPD-tetramers. Here, we describe a novel approach to transform these large datasets into user-friendly chord diagrams using R. This visualization process is straightforward, simple to implement, and accessible to inexperienced users that have never used R before. Combining CGPD-tetramers into a single chord diagram helps identify potential key chemicals, genes, phenotypes, and diseases. This visualization allows users to more readily analyze computational datasets that can fill the exposure knowledge gaps in the environmental health continuum.