bluuebunny/crossref_metadata_2025 huggingface dataset:
Advanced genetic therapies for the treatment of Rett syndrome: state of the art and future perspectives
Authors: Palmieri Michela , Pozzer Diego , Landsberger Nicoletta
Published: May 2023

Loss and gain of functions mutations in the X-linked MECP2 (methyl-CpG-binding protein 2) gene are responsible for a set of generally severe neurological disorders that can affect both genders. In particular, Mecp2 deficiency is mainly associated with Rett syndrome (RTT) in girls, while duplication of the MECP2 gene leads, mainly in boys, to the MECP2 duplication syndrome (MDS). No cure is currently available for MECP2 related disorders. However, several studies have reported that by re-expressing the wild-type gene is possible to restore defective phenotypes of Mecp2 null animals. This proof of principle endorsed many laboratories to search for novel therapeutic strategies to cure RTT. Besides pharmacological approaches aimed at modulating MeCP2-downstream pathways, genetic targeting of MECP2 or its transcript have been largely proposed. Remarkably, two studies focused on augmentative gene therapy were recently approved for clinical trials. Both use molecular strategies to well-control gene dosage. Notably, the recent development of genome editing technologies has opened an alternative way to specifically target MECP2 without altering its physiological levels. Other attractive approaches exclusively applicable for nonsense mutations are the translational read-through (TR) and t-RNA suppressor therapy. Reactivation of the MECP2 locus on the silent X chromosome represents another valid choice for the disease. In this article, we intend to review the most recent genetic interventions for the treatment of RTT, describing the current state of the art, and the related advantages and concerns. We will also discuss the possible application of other advanced therapies, based on molecular delivery through nanoparticles, already proposed for other neurological disorders but still not tested in RTT.
Behavioral and neuro-functional consequences of eliminating the KCNQ3 GABA binding site in mice
Authors: Chen Kiki J. , Yoshimura Ryan , Edmundo Clarissa Adriana , Truong Tri Minh , Civelli Olivier , Alachkar Amal , Abbott Geoffrey W.
Published: May 2023

Voltage-gated potassium (Kv) channels formed by α subunits KCNQ2-5 are important in regulating neuronal excitability. We previously found that GABA directly binds to and activates channels containing KCNQ3, challenging the traditional understanding of inhibitory neurotransmission. To investigate the functional significance and behavioral role of this direct interaction, mice with a mutated KCNQ3 GABA binding site (Kcnq3-W266L) were generated and subjected to behavioral studies. Kcnq3-W266L mice exhibited distinctive behavioral phenotypes, of which reduced nociceptive and stress responses were profound and sex-specific. In female Kcnq3-W266L mice, the phenotype was shifted towards more nociceptive effects, while in male Kcnq3-W266L mice, it was shifted towards the stress response. In addition, female Kcnq3-W266L mice exhibited lower motor activity and reduced working spatial memory. The neuronal activity in the lateral habenula and visual cortex was altered in the female Kcnq3-W266L mice, suggesting that GABAergic activation of KCNQ3 in these regions may play a role in the regulation of the responses. Given the known overlap between the nociceptive and stress brain circuits, our data provide new insights into a sex-dependent role of KCNQ3 in regulating neural circuits involved in nociception and stress, via its GABA binding site. These findings identify new targets for effective treatments for neurological and psychiatric conditions such as pain and anxiety.
Enhancement of agri-food by-products: green extractions of bioactive molecules with fungicidal action against mycotoxigenic fungi and their mycotoxins
Authors: Giorni Paola , Bulla Giulia , Leni Giulia , Soldano Mariangela , Tacchini Massimo , Guerrini Alessandra , Sacchetti Gianni , Bertuzzi Terenzio
Published: May 2023

Introduction

Today, alternative strategies based on the use of bioactive compounds have been proposed to reduce mycotoxin contamination and limit the use of chemical fungicides.

Methods

In the present work, several by-products collected from the agri-food chain (i.e., red and white grape marc, red grapevine leaves, grape seeds and stalks, pear, apple, green beans, tomato, and spent hops) were subjected to green extraction protocols (i.e., steam distillation, Ultrasound-Assisted, and Naviglio® extraction) to obtain extracts rich in polyphenols and terpenes. Each extract was assessed in vitro for its ability to inhibit the development of the main mycotoxigenic species and related mycotoxins.

Results and Discussion

Aspergillus flavus and A. carbonarius were significantly reduced by pear (from −45 to −47%) and grape marc (from −21 to −51%) extracts, while F. graminearum was shown to be highly influenced by grape stalk, pear, and grape marc extracts (−24% on average). On the contrary, F. verticillioides was inhibited only by pear (−18%) and to a very low and negligible extent by apple (−1%) and green beans (−3%). Regarding the reduction of mycotoxins, the extracts were able to inhibit OTA from 2 to 57%, AFB1 from 5 to 75%, and DON from 14 to 72%. The highest percentages of reduction were obtained against FBs (from 11 to 94%), ZEN (from 17 to 100%), and Alternaria toxins (from 7 to 96%). In conclusion, this work provided promising results for the production of bioactive extracts obtained from agri-food by-products, which could be exploited as potential biofungicides against the development of mycotoxigenic fungi and related mycotoxins.
SLC26 family: a new insight for kidney stone disease
Authors: Li Jialin , Huang Sigen , Liu Shengyin , Liao Xinzhi , Yan Sheng , Liu Quanliang
Published: May 2023

The solute-linked carrier 26 (SLC26) protein family is comprised of multifunctional transporters of substrates that include oxalate, sulphate, and chloride. Disorders of oxalate homeostasis cause hyperoxalemia and hyperoxaluria, leading to urinary calcium oxalate precipitation and urolithogenesis. SLC26 proteins are aberrantly expressed during kidney stone formation, and consequently may present therapeutic targets. SLC26 protein inhibitors are in preclinical development. In this review, we integrate the findings of recent reports with clinical data to highlight the role of SLC26 proteins in oxalate metabolism during urolithogenesis, and discuss limitations of current studies and potential directions for future research.
Adventitial macrophage accumulation impairs perivascular nerve function in mesenteric arteries with inflammatory bowel disease
Authors: Grunz Elizabeth A. , Jones Benjamin W. , Lateef Olubodun Michael , Sen Sidharth , Wilkinson Katie , Joshi Trupti , Boerman Erika M.
Published: May 2023

Introduction: Inflammatory bowel disease involves aberrant immune responses and is associated with both cardiovascular disease risk and altered intestinal blood flow. However, little is known about how inflammatory bowel disease affects regulation of perivascular nerves that mediate blood flow. Previous work found perivascular nerve function is impaired in mesenteric arteries with Inflammatory bowel disease. The purpose of this study was to determine the mechanism of impaired perivascular nerve function.

Methods: RNA sequencing was performed on mesenteric arteries from IL10−/− mice treated with H. hepaticus to induce disease (inflammatory bowel disease) or left non-gavaged (Control). For all other studies, Control and Inflammatory bowel disease mice received either saline or clodronate liposome injections to study the effect of macrophage depletion. Perivascular nerve function was assessed using pressure myography and electrical field stimulation. Leukocyte populations, and perivascular nerves, and adventitial neurotransmitter receptors were labeled using fluorescent immunolabeling.

Results: Inflammatory bowel disease was associated with increases in macrophage-associated gene expression, and immunolabeling showed accumulation of adventitial macrophages. Clodronate liposome injection eliminated adventitial macrophages, which reversed significant attenuation of sensory vasodilation, sympathetic vasoconstriction and sensory inhibition of sympathetic constriction in inflammatory bowel disease. Acetylcholine-mediated dilation was impaired in inflammatory bowel disease and restored after macrophage depletion, but sensory dilation remained nitric oxide independent regardless of disease and/or macrophage presence.

Conclusion: Altered neuro-immune signaling between macrophages and perivascular nerves in the arterial adventitia contributes to impaired vasodilation, particularly via dilatory sensory nerves. Targeting the adventitial macrophage population may help preserve intestinal blood flow in Inflammatory bowel disease patients.
Where on the face do we look during phonemic restoration: An eye-tracking study
Authors: Baron Alisa , Harwood Vanessa , Kleinman Daniel , Campanelli Luca , Molski Joseph , Landi Nicole , Irwin Julia
Published: May 2023

Face to face communication typically involves audio and visual components to the speech signal. To examine the effect of task demands on gaze patterns in response to a speaking face, adults participated in two eye-tracking experiments with an audiovisual (articulatory information from the mouth was visible) and a pixelated condition (articulatory information was not visible). Further, task demands were manipulated by having listeners respond in a passive (no response) or an active (button press response) context. The active experiment required participants to discriminate between speech stimuli and was designed to mimic environmental situations which require one to use visual information to disambiguate the speaker’s message, simulating different listening conditions in real-world settings. Stimuli included a clear exemplar of the syllable /ba/ and a second exemplar in which the formant initial consonant was reduced creating an /a/−like consonant. Consistent with our hypothesis, results revealed that the greatest fixations to the mouth were present in the audiovisual active experiment and visual articulatory information led to a phonemic restoration effect for the /a/ speech token. In the pixelated condition, participants fixated on the eyes, and discrimination of the deviant token within the active experiment was significantly greater than the audiovisual condition. These results suggest that when required to disambiguate changes in speech, adults may look to the mouth for additional cues to support processing when it is available.
Identity development and online and offline prosocial behaviors among early and middle adolescents
Authors: Iwasa Yasuhiro , Hihara Shogo , Ishizaki Kazuya , Yasui Genki , Hiro Makoto , Sugimura Kazumi
Published: May 2023

Research has demonstrated that adolescents of the digital age engage in developmental tasks by interacting with others in both online and offline environments. However, no studies have investigated how adolescents develop their identity, a crucial developmental task, by engaging in online and offline prosocial behaviors. To address this research gap, we examined the role of online and offline prosocial behavior in identity development during adolescence using variable- and person-centered approaches. The participants were 608 individuals in early adolescence (50.2% girls; age range = 12–13 years, Mage = 12.75 years, SD = 0.43) and 594 individuals in middle adolescence (50.3% girls; age range = 15–16 years, Mage = 15.79 years, SD = 0.41) in Japan. They completed questionnaires to measure identity development, online and offline prosocial behavior, and demographic characteristics. The results from the variable-centered approach (i.e., identity dimensions) revealed that both online and offline prosocial behaviors were positively related to commitments and proactive explorations in early and middle adolescence. The findings from the person-centered approach (i.e., identity statuses) demonstrated that early and middle adolescents with higher levels of online prosocial behavior were more likely to show searching moratorium than all other identity statuses, whereas those with higher levels of offline prosocial behavior were more likely to show achievement than troubled diffusion, carefree diffusion, and undifferentiated. Consistent with both variable- and person-centered approaches, these findings highlight that online prosocial behavior can be a new resource for identity development in adolescence. Moreover, the results suggest that online prosocial behaviors lead to identity status in the process of maturing identity and that offline prosocial behavior is necessary to become more mature identity status. Regarding practical implications, educating adolescents on digital media literacy, including supportive behavior in online environments, is crucial to gradually exploring their identity. In addition, for adolescents to develop more mature identity, adults should create in-person environments in which they participate in offline prosocial behavior. The limitations of our findings with respect to the online and offline prosocial behavior scale items are discussed.
Occupational stress of elementary school teachers after eased COVID-19 restrictions: a qualitative study from China
Authors: Yao Yujing , Xu Jie
Published: May 2023

Background

On December 7, 2022, China optimized its virus response and significantly shifted its epidemic policy by downgrading COVID management and gradually restoring offline teaching in schools. This shift has brought many impacts on teachers.

Aims

Through qualitative research of thematic analysis, this paper studies the occupational pressure of primary school teachers in China after the shift in epidemic policy.

Methods

Two recruitment methods are adopted for this study. One was to email the principals of several primary schools in Zhejiang Province to introduce the research project and indicate the idea of recruiting participants. With their help, we have found teachers who volunteer to participate. The second was to release recruitment information in the network forum (e.g., online teacher forums) to find volunteer participants. Through semi-structured interviews and diaries, 18 primary school teachers from different regions and schools in Zhejiang Province were interviewed. All responses in the interviews were transcribed anonymously. Braun and Clarke’s thematic analysis was used to analyze the participants’ responses.

Results

Eighteen participants took part in the research project. Forty-five final codes, generated from 89 codes initially obtained from the dataset, are classified into five final themes: uncertainty, overburdened, neglected, worry about students, and influence, which reflect the professional stress of primary school teachers following the epidemic prevention policies relaxed.

Conclusion

Five themes were identified in the research. The problems described by the participants include burdensome offline activities, being disturbed out of hours, and appearing understaffed for the infection. These problems harmed the participants’ mental health, including anxiety, fatigue, stress, and other adverse psychological conditions. Awareness and attention to the psychological situation of primary school teachers after the eased COVID control are crucial. We believe protecting teachers’ mental health is necessary, especially in this particular period.
Understanding the effect of angina on general and dimensions of psychological distress: findings from understanding society
Authors: Kang Weixi
Published: May 2023

Background

The current study aimed to examine how the general and dimensions of psychological distress are affected by angina.

Methods

First, a confirmatory factor analysis (CFA) was used to produce the three-factor solution of the GHQ-12. Second, a predictive normative modeling approach to predict the expected scores for 1,081 people with angina based on a model trained on demographics from 8,821 age and sex-matched people without angina. Finally, one-sample t-tests were used to determine the differences between the actual psychological distress scores and expected psychological distress scores in participants with angina.

Results

There were three underlying structures of the GHQ-12 labeled as GHQ-12A (social dysfunction & anhedonia), GHQ-12B (depression & anxiety), and GHQ-12C (loss of confidence). Moreover, participants with angina had more psychological distress as indicated by the GHQ-12 summary score (Cohen’s d = 0.31), GHQ-12A (Cohen’s d = 0.34), GHQ-12B (Cohen’s d = 0.21), and GHQ-12C (Cohen’s d = 0.20) comparing to controls.

Conclusion

The current study implies that GHQ-12 is a valid measure of psychological distress in people with angina, and there is a need to consider the dimensions of psychological distress in angina rather than solely focusing on certain dimensions of psychological distress such as depression or anxiety issues in people with angina. Clinicians should come up with interventions to reduce psychological distress in people with angina which can then lead to better outcomes.
Retention rate in methadone maintenance treatment and factors associated among referred patients from the compulsory residential centers compared to voluntary patients
Authors: Radfar Niayesh , Radfar Seyed Ramin , Mohammadi Faezeh , Azimi Amir , Amirkafi Ali , Tehrani-Banihashemi Arash
Published: May 2023

Introduction

Compulsory treatment has decades of history in Iran; both before and after the Islamic Revolution, but there are many debates regarding its efficacy and effectiveness. Retention Rate is one of the best indices to estimate the efficacy of treatment. This study will compare Retention Rate among people referred from compulsory treatment centers and volunteer participants.

Methods

This was a retrospective (historical) cohort study that has been conducted among people who were taking methadone maintenance treatment (MMT). The study sample was selected from the MMT centers that admit both referral patients from compulsory centers and voluntary patients. All newly admitted patients from March 2017 to March 2018 were enrolled and followed up until March 2019.

Results

A total of 105 participants were recruited for the study. All were males with a mean age of 36.6 ± 7.9 years. Fifty-six percent of individuals were referred from compulsory residential centers. The total one-year retention rate of participants in this study was 15.84%. The one-year retention rate for the patients referred from compulsory residential centers and the non-referred patients was 12.28 and 20.45%, respectively (value of p = 0.128). Among the other studied factors, only marital status was significantly associated with MMT retention (p = 0.023).

Conclusion

Although the average treatment adherence time for non-referred patients was about 60 days higher than those referred from compulsory residential centers, this study found no significant differences in retention days and a one-year retention rate. Further studies with larger sample sizes and longer follow-ups are needed to explore the efficacy of compulsory treatment methods in Iran.
Intermittent theta burst stimulation to the left dorsolateral prefrontal cortex improves cognitive function in polydrug use disorder patients: a randomized controlled trial
Authors: Dong Ling , Chen Wen-Cai , Su Hang , Wang Mei-Ling , Du Cong , Jiang Xing-ren , Mei Shu-fang , Chen Si-Jing , Liu Xiu-Jun , Liu Xue-Bing
Published: May 2023

Background

Polydrug abuse is common among opioid users. Individuals who use both heroin and methamphetamine (MA) have been shown to experience a wide range of cognitive deficits. Previous research shows that repetitive transcranial magnetic stimulation (rTMS) can change cerebral cortical excitability and regulate neurotransmitter concentration, which could improve cognitive function in drug addiction. However, the stimulation time, location, and possible mechanisms of rTMS are uncertain.

Methods

56 patients with polydrug use disorder were randomized to receive 20 sessions of 10 Hz rTMS (n = 19), iTBS (n = 19), or sham iTBS (n = 18) to the left DLPFC. All patients used MA and heroin concurrently. Cognitive function was assessed and several related proteins including EPI, GABA-Aα5, IL-10, etc. were quantified by ELISA before and after the treatment.

Results

Baseline RBANS scores were lower than normal for age (77.25; IQR 71.5–85.5). After 20 treatment sessions, in the iTBS group, the RBANS score increased by 11.95 (95% CI 0.02–13.90, p = 0.05). In particular, there were improvements in memory and attention as well as social cognition. Following treatment, serum EPI and GABA-Aα5 were reduced and IL-10 was elevated. The improvement of immediate memory was negatively correlated with GABA-Aα5 (r = −0.646, p = 0.017), and attention was positively correlated with IL-10 (r = 0.610, p = 0.027). In the 10 Hz rTMS group, the improvement of the RBANS total score (80.21 ± 14.08 before vs.84.32 ± 13.80 after) and immediate memory (74.53 ± 16.65 before vs.77.53 ± 17.78 after) was statistically significant compared with the baseline (p < 0.05). However, compared with the iTBS group, the improvement was small and the difference was statistically significant. There was no statistically significant change in the sham group (78.00 ± 12.91 before vs.79.89 ± 10.92 after; p > 0.05).

Conclusion

Intermittent theta burst stimulation to the left DLPFC may improve cognitive function in polydrug use disorder patients. Its efficacy appears to be better than that of 10 Hz rTMS. The improvement of cognitive function may be related to GABA-Aα5 and IL-10. Our findings preliminarily demonstrate the clinical value of iTBS to the DLPFC to augment neurocognitive recovery in polydrug use disorders.
Determinants of quality of life in primary family caregivers of patients with advanced cancer: a comparative study in southern China
Authors: Lin Jiaqi , He Zhuoxin , Fan Guanhua
Published: May 2023

Objective

To examine and compare the quality of life (QoL) of the primary family caregivers (PFCs) of inpatients with advanced cancer and the PFCs of home hospice patients with advanced cancer and to analyze the determinants of QoL.

Methods

Four hospices and three comprehensive or tumor hospitals in Guangdong Province, China were research sites. QoL was measured using paper-based and online questionnaires. Multiple stepwise linear regression was used to analyze the determinants of QoL of PFCs.

Results

The PFCs of inpatients had significantly better QoL than did the PFCs of home hospice patients (p < 0.01). One-way ANOVA results indicated the following: for the PFCs of inpatients, PFC age (t = 2.411, p < 0.05), type of relationship with patient (F = 2.985, p < 0.05), and family economic situation (F = 3.423, p < 0.05) significantly affected PFCs’ QoL; for the PFCs of home hospice patients, family economic situation (F = 3.757, p < 0.05) and care experience (t = 2.021, p < 0.05) significantly affected PFCs’ QoL. A multiple stepwise linear regression was conducted: for the PFCs of inpatients, family economic situation and whether the PFC was the patient’s immediate family member were included as predictors of QoL; for the PFCs of home hospice patients, family economic situation and care experience were included as predictors of QoL.

Conclusion

Our findings can help improve the home hospice care service model in mainland China. In particular, the QoL of the PFCs of home hospice patients requires urgent attention. The PFCs of home hospice patients requires more nursing guidance and interactions with community.
Number of medications and polypharmacy are associated with frailty in older adults: results from the Midlife in the United States study
Authors: Alqahtani Bader
Published: May 2023

Objectives

The current study aimed to examine the association between the number of medications, polypharmacy, and frailty in community-dwelling older adults. In addition, the cutoff score for the number of medications related with frailty in this sample was determined.

Methods

A cross-sectional analysis was performed using data of 328 individual aged between 65 and 85 years from the Midlife in the United States (MIDUS 2): Biomarker Project, 2004–2009, a multisite longitudinal study, for 328 individuals aged between 65 and 85 years. All the participants were categorized into two groups based on the number of medications used: no polypharmacy (n = 206) and polypharmacy (n = 122). The polypharmacy was defined as having 5 or more medication per day. Frailty status was measured using a modified form of Fried frailty phenotype through the presences of the following indicators include low physical activity; exhaustion; weight loss; slow gait speed and muscle weakness. Participants were categorized into three different groups based on total score: 0 as robust, 1 to 2 as prefrail, 3 or more as frail. The relationship between no. of medications, polypharmacy, and frailty was examined using a multinomial logistic regression model. The model was adjusted for age, sex, BMI, and no. of chronic conditions. Receiver operator characteristics and area under the curve were used to determine the cutoff number of medications.

Results

Number of medications, and polypharmacy were associated with being frail (relative risk ratio [RRR]: 1.30; 95% confidence interval [CI]: [1.12, 1.50], p = 0.001), (RRR: 4.77; 95% CI [1.69, 13.4], p = 0.003), respectively. Number of medications with cutoff 6 medication or more was associated with being in frail category with sensitivity of 62% and specificity of 73%.

Conclusion

Polypharmacy was shown to be significantly related to frailty. A cutoff score of 6 or more medications distinguished frail from non-frail. Addressing polypharmacy in the older population might ameliorate the impact of physical frailty.
Parental control and adolescent internet addiction: the moderating effect of parent-child relationships
Authors: Zhu Xiaoqin , Deng Chen , Bai Wanyue
Published: May 2023

Introduction

The present study investigated how maternal and paternal controls, including behavioral and psychological controls, predict adolescent Internet addiction, as well as the potential moderating effects of adolescent gender and parent-child relationships on the predictions.

Methods

Data were collected from 1,974 Chinese adolescents (age range = 14–22; mean = 16.47; SD = 0.87; 1,099 girls) in Guizhou Province, mainland China in November 2021. Internet addiction was measured using the ten-item Internet Addiction Test developed by Kimberly Young, and Parental control and parent-child relationships were measured by the respective subscales derived from the validated Chinese Parent-Child Subsystem Quality Scale.

Results

Hierarchical regression analyses revealed that after the covariates were statistically controlled, both parents' behavioral controls showed significant negative predictions on adolescent Internet addiction, while their psychological control tended to positively predict Internet addiction among adolescents, although the effect was only marginal. In addition, the impacts of maternal and paternal controls were equal, and such impacts did not vary between sons and daughters. While adolescent gender was not a significant moderator, the parent-child relationship quality significantly moderated the effects of paternal behavioral control, paternal psychological control, and maternal psychological control on adolescents' Internet addiction. Specifically, the prediction of paternal behavioral control was stronger while the effect of paternal and maternal psychological control was weaker among adolescents with a positive father-child relationship than those with a moderate or poor father-child relationship.

Discussion

These findings indicate the protective function of parents' behavioral control and the negative impact of psychological control on the development of adolescent Internet addiction. Further, a positive relationship between the father and the adolescent can strengthen the positive effect of paternal behavioral control and mitigate the negative effects of both parents' psychological controls.
Reliability and validity of Polar Team Pro measurements in running at different velocities in an indoor setting
Authors: van den Tillaar Roland , Gaustad Pettersen Fredrik , Lagestad Pål
Published: May 2023

The purpose of this study was to test the reliability and validity of Polar Team Pro measurements of velocity, acceleration, and distance covered in a rectangular run at different intensities in an indoor setting. In two test sessions, 10 women (age 15.7 ± 0.4 years, body mass 61.3 ± 5.3 kg, body height 1.69 ± 0.07 m) performed 100 m runs at different intensities, ranging from 8 to 18 km/h. The 100 m runs were performed on a rectangular track at an indoor handball facility. The main finding revealed that Polar Team Pro underestimated the running distance and velocity (10%–15% at 10 km/h), especially at higher speeds (15% and 6% at 15 and 18 km/h, respectively). Between test days, coefficients of variance varied from 4.2% to 12.4%, when measuring at different speeds. However, a significant difference was found for the two runs only at 15 km/h between the two test days. It was concluded that Polar Team Pro underestimated the running distance and velocity when measuring a rectangular run at different speeds in an indoor setting, especially at higher speeds. This underestimation is probably caused by the inaccuracy of the inertial measurement unit algorithm that calculates the distance, as body height influences the distance and velocity measurements. The variability between the different units is, thereby, also influenced, causing variable coefficients of variance between the sensors. Test–retest variability was acceptable. Based on the findings of this study, practitioners should be cautious when measuring speed and distance using Polar Team Pro Sensors in indoor settings, as these measurements are underestimated with increasing speed.
Intraductal papillary mucinous neoplasm of the intrahepatic bile duct: a review of literature and a rare case report
Authors: Zibari Lehat , Naseer Muhammad S. , Patel Het , Shokouh-Amiri Hosein , Wellman Gregory , Dies David , Browne Veron , Zibari Gazi B.
Published: May 2023

Background

Intraductal papillary neoplasm of the bile duct is a rare variant of bile duct tumors, which is characterized by papillary or villous growth inside the bile duct. Having papillary and mucinous features such as those found in pancreatic intraductal papillary mucinous neoplasm (IPMN) is extremely rare. We report a rare case of intraductal papillary mucinous neoplasm of the intrahepatic bile duct.

Case report

A 65-year-old male Caucasian with multiple comorbidities presented to the emergency room with moderate constant pain at the right upper quadrant (RUQ) abdomen for the last several hours. On physical examination, he was found to have normal vital signs, with icteric sclera and pain on deep palpation at the RUQ region. His laboratory results were significant for jaundice, elevated liver function tests and creatinine, hyperglycemia, and leukocytosis. Multiple imaging studies revealed a 5 cm heterogeneous mass in the left hepatic lobe that demonstrated areas of internal enhancement, mild gall bladder wall edema, dilated gall bladder with mild sludge, and 9 mm common bile duct (CBD) dilatation without evidence of choledocholithiasis. He underwent a CT-guided biopsy of this mass, which revealed intrahepatic papillary mucinous neoplasm. This case was discussed at the hepatobiliary multidisciplinary conference, and the patient underwent an uneventful robotic left partial liver resection, cholecystectomy, and lymphadenectomy.

Conclusion

IPMN of the biliary tract may represent a carcinogenesis pathway different from that of CBD carcinoma arising from flat dysplasia. Complete surgical resection should be performed whenever possible because of its significant risk of harboring invasive carcinoma.
Assessing the effect of a canine surgical-neutering educational programme on the knowledge and confidence of Indian veterinary participants
Authors: Rayner Emma L. , Airikkala-Otter Ilona , Mellanby Richard J. , Gibson Andrew D. , Susheelan Aswin , Gamble Luke , Mazeri Stella
Published: May 2023

India has a large, free-roaming dog population, encompassing both owned and stray dogs. Canine surgical neutering is often a central component of dog population management and rabies control initiatives. The provision of practical, surgical training opportunities remains a major challenge for veterinary educational establishments worldwide to ensure competency in this routine procedure. A 12-day educational programme, focusing on surgical neutering skills, was developed to address this need. A questionnaire comprising 26 questions covering surgical and clinical topics, and a self-assessment of confidence in undertaking five common surgical procedures, was completed immediately before and after finishing the programme. A total of 296 participants attended, with 228 achieving the inclusion criteria for the study. Total knowledge scores increased significantly after the training programme (mean score pre-18.94, 95% CI 18.13–19.74; post-28.11, 95% CI 27.44–28.77, p < 0.05) with improvements seen in all categories (surgical principles, anaesthesia, antibiotic use and wound management). After accounting for other participants’ characteristics, scores increased, on average, by 9 points after training. Being female was associated with significantly higher overall scores, while compared to younger and older age groups, those aged 25–34 were associated with lower overall scores. Amongst those with post-graduate qualifications, overall scores increased with age. Furthermore, there was an increase in self-rated confidence by participants in undertaking all five procedures. This study demonstrates that a targeted training programme can improve veterinary participants’ knowledge and confidence in canine surgical neutering and may provide an effective way to develop surgical expertise amongst veterinarians engaged in dog population management initiatives.
Distributed GNE-Seeking under Partial Information Based on Preconditioned Proximal-Point Algorithms
Authors: Wang Zhongzheng , Li Huaqing , Chen Menggang , Tang Jialong , Cheng Jingran , Shi Yawei
Published: May 2023

This paper proposes a distributed algorithm for games with shared coupling constraints based on the variational approach and the proximal-point algorithm. The paper demonstrates the effectiveness of the proximal-point algorithm in distributed computing of generalized Nash equilibrium (GNE) problems using local data and communication with neighbors in any networked game. The algorithm achieves the goal of reflecting local decisions in the Nash–Cournot game under partial-decision information while maintaining the distributed nature and convergence of the algorithm.
Design, Modelling, and Experimental Validation of a Glass U-Tube Mass Sensing Cantilever for Particulate Direct-on-Line Emissions Measurement
Authors: Nicklin Daniel , Gohari Darabkhani Hamidreza
Published: May 2023

The requirement to monitor and control industrial processes has increased over recent years, therefore innovative techniques are required to meet the demand for alternative methods of particulate measurement. Resonant mass sensors are now strong candidates for accurate mass measurement and are frequently used in many diverse fields of science and engineering. This paper presents the design, modelling, and optimal geometry selection for sensitivity improvement of a U-shaped glass tube as a resonant mass sensing cantilever with a view to becoming a component of particulate measurement equipment. Finite Element Analysis (FEA) was used to develop the system which was validated experimentally using a physical model. This paper focuses on both the proof of concept and the geometry selection of the sensor using analysis of the system sensitivity for best selection. Modal and harmonic analysis were undertaken across a range of commercially available glass tube sizes from 6 mm to 10 mm diameter, to determine the optimal geometry selection, validated with practical experimental data. Results show a consistent difference of 3–5% between the simulation and experimental results, showing strong correlation. This research provides a methodology on the development of using a U-shaped glass tube for accurate mass measurement with a view to exploring the design as a component of particulate emissions equipment. The experimental and simulation results confirm that the highest sensitivity is achieved when the geometry dimensions, and therefore the vacant mass of the tube, is reduced. The 6 mm diameter tube with the smallest bend radius was the most suitable design to meet the design criteria. The calibration curve was plotted to allow an unknown mass to be calculated, which gave an R2 value of 0.9984. All experimental work was repeated three times with results giving an average of 0.44% between the minimum and maximum showing strong linearity and suggesting the potential for implementation of the methodology in its intended application. The design provides possible solutions to some of the issues currently seen with particulate measurement from stationary sources.
Impacts of Climate and Anthropogenic Disturbances on Vegetation Structure and Functions
Authors: Zhang Wentao , Wu Shuyao
Published: May 2023

Vegetation serves as a habitat for various wildlife species, provides crucial ecosystem services to society, and plays a critical role in regulating the global climate [...]
(HIIT-The Track) High-Intensity Interval Training for People with Parkinson’s Disease: Individual Response Patterns of (Non-)Motor Symptoms and Blood-Based Biomarkers—A Crossover Single-Case Experimental Design
Authors: Gomes Elvira S. Amaral , Van den Heuvel Odile A. , Rietberg Marc B. , De Groot Vincent , Hirsch Mark A. , Van de Berg Wilma D. J. , Jaspers Richard T. , Vriend Chris , Vanbellingen Tim , Van Wegen Erwin E. H.
Published: May 2023

Introduction: Physical exercise is receiving increasing interest as an augmentative non-pharmacological intervention in Parkinson’s disease (PD). This pilot study primarily aimed to quantify individual response patterns of motor symptoms to alternating exercise modalities, along with non-motor functioning and blood biomarkers of neuroplasticity and neurodegeneration. Materials & Methods: People with PD performed high-intensity interval training (HIIT) and continuous aerobic exercise (CAE) using a crossover single-case experimental design. A repeated assessment of outcome measures was conducted. The trajectories of outcome measures were visualized in time series plots and interpreted relative to the minimal clinically important difference (MCID) and smallest detectable change (SDC) or as a change in the positive or negative direction using trend lines. Results: Data of three participants were analyzed and engaging in physical exercise seemed beneficial for reducing motor symptoms. Participant 1 demonstrated improvement in motor function, independent of exercise modality; while for participant 2, such a clinically relevant (positive) change in motor function was only observed in response to CAE. Participant 3 showed improved motor function after HIIT, but no comparison could be made with CAE because of drop-out. Heterogeneous responses on secondary outcome measures were found, not only between exercise modalities but also among participants. Conclusion: Though this study underpins the positive impact of physical exercise in the management of PD, large variability in individual response patterns to the interventions among participants makes it difficult to identify clear exercise-induced adaptations in functioning and blood biomarkers. Further research is needed to overcome methodological challenges in measuring individual response patterns.
Indoleamine 2,3-Dioxygenase as a Therapeutic Target for Alzheimer’s Disease and Geriatric Depression
Authors: Savonije Karl , Meek Autumn , Weaver Donald F.
Published: May 2023

Neuroimmune-triggered neuroinflammation of the central nervous system is emerging as an important aetiopathogenic factor for multiple neurological disorders, including depression, dementia, Alzheimer’s disease, multiple sclerosis and others. Tryptophan metabolism via the kynurenic pathway, which is initiated by the indoleamine-2,3-dioxygenase (IDO-1) enzyme, is a key regulator of the neuroimmune system and its associated neuroinflammatory effects. As discussed in this review, targeting the production of immunopathic and potentially neurotoxic kynurenine metabolites by inhibitory downregulation of IDO-1 may prove a viable target against inflammation-induced neurological conditions, particularly depression and dementia.
Endolymphatic Hydrops Magnet Resonance Imaging in Ménière’s Disease Patients after Cochlea Implantation
Authors: Pfeiffer Christoph J. , Gehl Hans-Björn , Scholtz Lars-Uwe , Goon Peter , Sudhoff Holger , Todt Ingo
Published: May 2023

Introduction: Cochlear implantation in patients with Ménière’s disease (MD) is the treatment of choice in cases of functional deafness. Additional vertigo control is of central importance in this group of patients. Endolymphatic hydrops (ELH) is the pathophysiological correlate of MD and can be evaluated by magnet resonance imaging (MRI). Bilateral MD occurs in 10–33% and can be the reason for a postoperative persisting or newly occurring vertigo in this group. Recent developments in the field of implant magnets and experience in MRI sequences allow the diagnostic performance of MRI in cochlear implantees to be evaluated. The aim of the present study was to evaluate the possibility of MRI as a visual diagnostic tool for endolymphatic hydrops in cochlear implantees. Material and Methods: This was a retrospective study including three cochlear implantees (age: 61–76 years, one female, two male) suffering from MD who, postoperatively, had a recurrence of vertigo with Ménière’s-like symptoms. An MRI was performed for the evaluation of ELH (ELH-MRI). MRI observation was performed by a 4 h iv. delayed Gad 3 D Flair sequence. Results: In all cases, the ipsilateral implant magnet artifact covered the vestibulum, the semicircular canals and the cochlea. The contralateral vestibulum, the semicircular canal and the cochlea were fully observable, and a classification of the ELH-MRI could be performed. Conclusion: ELH-MRI scanning allows for the detection of contralateral labyrinthine endolymphatic hydrops and is a tool for the postoperative evaluation of vertigo in cochlear implantees.
TERT Expression Induces Resistance to BRAF and MEK Inhibitors in BRAF-Mutated Melanoma In Vitro
Authors: Delyon Julie , Vallet Anaïs , Bernard-Cacciarella Mélanie , Kuzniak Isabelle , Reger de Moura Coralie , Louveau Baptiste , Jouenne Fanélie , Mourah Samia , Lebbé Céleste , Dumaz Nicolas
Published: May 2023

Because BRAF-mutated melanomas are addicted to the Mitogen Activated Protein Kinase (MAPK) pathway they show a high response rate to BRAF and MEK inhibitors. However, the clinical responses to these inhibitors are often short-lived with the rapid onset of resistance to treatment. Deciphering the molecular mechanisms driving resistance has been the subject of intense research. Recent in vitro and clinical data have suggested a link between expression of telomerase and resistance to targeted therapy in melanoma. TERT promoter mutations are the main mechanism for the continuous upregulation of telomerase in melanoma and co-occur frequently with BRAF alterations. To understand how TERT promoter mutations could be associated with resistance to targeted therapy in melanoma, we conducted translational and in vitro studies. In a cohort of V600E-BRAF-mutated melanoma patients, we showed that the TERT promoter mutation status and TERT expression tended to be associated with response to BRAF and MEK inhibitors. We demonstrated that TERT overexpression in BRAF-mutated melanoma cells reduced sensitivity to BRAF and MEK independently of TERT’s telomer maintenance activity. Interestingly, inhibition of TERT reduced growth of BRAF-mutated melanoma including resistant cells. TERT expression in melanoma can therefore be a new biomarker for resistance to MAPK inhibitors as well as a novel therapeutic target.
Outcomes of Penta-Refractory Multiple Myeloma Patients Treated with or without BCMA-Directed Therapy
Authors: Atrash Shebli , Mammadzadeh Aytaj , Peng Fulei , Alkharabsheh Omar , Afrough Aimaz , Cui Wei , Mahmoudjafari Zahra , Abdallah Al-Ola , Hashmi Hamza
Published: May 2023

Despite advances in treatment, outcomes remain poor for patients with penta-relapsed refractory multiple myeloma (RRMM). In this retrospective analysis, we evaluated the survival outcomes of penta-RRMM patients treated with (BCMA)- directed therapy (BDT). We identified 78 patients with penta-RRMM. Median age was 65 years, 29 (37%) had R-ISS stage III disease, 63 (81%) had high-risk cytogenetics, and 45 (58%) had extra-medullary disease. Median LOT prior to penta-refractory state was 5 (3–12). Amongst penta-RRMM, 43 (55%) were treated with BDT, 35 (45%) were not treated with BDT. Type of BDT received included belantamab mafadotin 15 (35%), Chimeric Antigen Receptor T-cell therapy 9 (21%), BCMA monoclonal antibody 6 (14%), and Bispecific T-cell engager 2 (5%). Eleven (25%) patients received more than one BDT. No significant differences were identified between baseline characteristics for the two groups. Patients treated with a BDT had better median overall survival, 17 vs. 6 months, HR 0.3 p-value < 0.001. Poor performance status, white race, and high-risk cytogenetics were associated with worse outcomes, whereas using a BDT was associated with better outcomes. Patients with penta-refractory MM have poor outcomes. Our retrospective analysis showed a significant survival benefit using BDT when compared to non-BDT for patients with penta-RRMM.
Is There Really a Difference in Outcomes between Men and Women with Hepatocellular Cancer?
Authors: Fa Andrea , Danos Denise M. , Maniscalco Lauren , Yi Yong , Wu Xiao-Cheng , Maluccio Mary A. , Chu Quyen D. , Lyons John M.
Published: May 2023

Hepatocellular carcinoma (HCC) is a male-dominated disease. Currently, gender differences remain incompletely defined. Data from the state tumor registry were used to investigate differences in demographics, comorbidities, treatment patterns, and cancer-specific survival (HSS) among HCC patients according to gender. Additional analyses were performed to evaluate racial differences among women with HCC. 2627 patients with HCC were included; 498 (19%) were women. Women were mostly white (58%) or African American (39%)—only 3.8% were of another or unknown race. Women were older (65.1 vs. 61.3 years), more obese (33.7% vs. 24.2%), and diagnosed at an earlier stage (31.7% vs. 28.4%) than men. Women had a lower incidence of liver associated comorbidities (36.1% vs. 43%), and more often underwent liver-directed surgery (LDS; 27.5% vs. 22%). When controlling for LDS, no survival differences were observed between genders. African American women had similar HSS rates compared to white women (HR 1.14 (0.91,1.41), p = 0.239) despite having different residential and treatment geographical distributions. African American race and age >65 were predictive for worse HSS in men, but not in women. Overall, women with HCC undergo more treatment options—likely because of the earlier stage of the cancer and/or less severe underlying liver disease. However, when controlling for similar stages and treatments, HCC treatment outcomes were similar between men and women. African American race did not appear to influence outcomes among women with HCC as it did in men.