bluuebunny/crossref_metadata_2025 huggingface dataset:
The first COVID-19 new graduate nurses generation: findings from an Italian cross-sectional study
Authors: Palese Alvisa , Brugnolli Anna , Achil Illarj , Mattiussi Elisa , Fabris Stefano , Kajander-Unkuri Satu , Dimonte Valerio , Grassetti Luca , Danielis Matteo
Published: May 2022

Background

Nursing education has been disrupted by the onset of the COronaVIrus Disease 19 (COVID-19) pandemic, potentially impacting learning experiences and perceived competencies at the time of graduation. However, the learning experiences of students since the onset of COVID-19, their perceived competences achieved and the employment status one month after graduation, have not been traced to date.

Methods

A cross sectional online survey measured the individual profile, the learning experience in the last academic year and the perceived competences of the first COVID-19 new nursing graduates in two Italian universities. Details relating to employment status and place of employment (Covid-19 versus non-COVID-19 units) one month after graduation were also collected and the data compared with those reported by a similar cohort of new graduates pre-pandemic in 2018–2019. All those who graduated in November 2020 and attended their third year after the onset of the COVID-19 pandemic were eligible. The online survey included individual, nursing programme and first working experience variables alongside the Nurse Competence Scale (NCS). Descriptive and inferential statistical analyses were performed.

Results

A total of 323 new graduates participated. In their last academic year, they experienced a single, long clinical placement in non-COVID-19 units. One month after graduation, 54.5% (n = 176) were working in COVID-19 units, 22.9% (n = 74) in non-COVID-19 units and 22.6 (n = 73) were unemployed. There was no statistical difference among groups regarding individual variables and the competences perceived. Fewer new graduates working in COVID-19 units experienced a transition programme compared to those working in non-COVID-19 units (p = 0.053). At the NCS, the first COVID-19 new graduate generation perceived significantly lower competences than the pre-COVID-19 generation in the ‘Helping role’ factor and a significant higher in ‘Ensuring quality’ and ‘Therapeutic interventions’ factors.

Conclusions

The majority of the first COVID-19 new graduate generation had been employed in COVID-19 units without clinical experience and transition programmes, imposing an ethical debate regarding (a) the role of education in graduating nurses in challenging times with limited clinical placements; and (b) that of nurse managers and directors in ensuring safe transitions for new graduates. Despite the profound clinical placement revision, the first COVID-19 new graduate generation reported competences similar to those of the pre-COVID-19 generation, suggesting that the pandemic may have helped them to optimise the clinical learning process.
Use of outpatient and inpatient health care services by occupation—a register study of employees in Oulu, Finland
Authors: Rinne Hanna , Laaksonen Mikko , Blomgren Jenni
Published: May 2022

Background

The aim of this study was to examine how the use of outpatient and inpatient health services differs by occupational groups, and whether the differences are explained by sociodemographic factors and health status.

Methods

We used register-based data on 25–64-year-old employees living in the city of Oulu, Finland, in 2018 (N = 61,848). Use of outpatient health care services (public, private and occupational health care) among men and women was analysed with negative binomial regression models, and use of inpatient health care with logistic regression models, using two occupational classifications: occupational group (1-digit level) and more detailed occupation (2-digit level). Adjusted covariates were age, education, income, marital status, special reimbursement entitlements for medicines, and sickness absence.

Results

Examined at the level of larger occupational groups, the use of outpatient and inpatient health care was less common than average among managers, professionals and skilled agricultural, forestry and fishery workers; in women also among craft and related trades workers. Controlling for covariates explained only part of the differences, more among women than among men. Analysed at the level of more detailed occupations, the adjusted use of outpatient and inpatient care was more common among health associate professionals and stationary plant and machine operators, both among men and women. Furthermore, the use of outpatient care was common among male personal care workers, protective service workers and metal, machinery and related trades workers as well as among labourers in mining, construction, manufacturing and transport, and female customer services clerks and sales workers.

Conclusion

The use of health care services differs by occupation, and the differences are not fully explained by sociodemographic factors and health status. High occupational risks, attitudes and knowledge may explain the more frequent use of health services. Furthermore, explanations may be sought from lack of access to occupational health care or healthier working conditions and behavior.
A deep learning approach identifies new ECG features in congenital long QT syndrome
Authors: Aufiero Simona , Bleijendaal Hidde , Robyns Tomas , Vandenberk Bert , Krijger Christian , Bezzina Connie , Zwinderman Aeilko H. , Wilde Arthur A. M. , Pinto Yigal M.
Published: May 2022

Background

Congenital long QT syndrome (LQTS) is a rare heart disease caused by various underlying mutations. Most general cardiologists do not routinely see patients with congenital LQTS and may not always recognize the accompanying ECG features. In addition, a proportion of disease carriers do not display obvious abnormalities on their ECG. Combined, this can cause underdiagnosing of this potentially life-threatening disease.

Methods

This study presents 1D convolutional neural network models trained to identify genotype positive LQTS patients from electrocardiogram as input. The deep learning (DL) models were trained with a large 10-s 12-lead ECGs dataset provided by Amsterdam UMC and externally validated with a dataset provided by University Hospital Leuven. The Amsterdam dataset included ECGs from 10000 controls, 172 LQTS1, 214 LQTS2, and 72 LQTS3 patients. The Leuven dataset included ECGs from 2200 controls, 32 LQTS1, and 80 LQTS2 patients. The performance of the DL models was compared with conventional QTc measurement and with that of an international expert in congenital LQTS (A.A.M.W). Lastly, an explainable artificial intelligence (AI) technique was used to better understand the prediction models.

Results

Overall, the best performing DL models, across 5-fold cross-validation, achieved on average a sensitivity of 84 ± 2%, 90 ± 2% and 87 ± 6%, specificity of 96 ± 2%, 95 ± 1%, and 92 ± 4%, and AUC of 0.90 ± 0.01, 0.92 ± 0.02, and 0.89 ± 0.03, for LQTS 1, 2, and 3 respectively. The DL models were also shown to perform better than conventional QTc measurements in detecting LQTS patients. Furthermore, the performances held up when the DL models were validated on a novel external cohort and outperformed the expert cardiologist in terms of specificity, while in terms of sensitivity, the DL models and the expert cardiologist in LQTS performed the same. Finally, the explainable AI technique identified the onset of the QRS complex as the most informative region to classify LQTS from non-LQTS patients, a feature previously not associated with this disease.

Conclusions

This study suggests that DL models can potentially be used to aid cardiologists in diagnosing LQTS. Furthermore, explainable DL models can be used to possibly identify new features for LQTS on the ECG, thus increasing our understanding of this syndrome.
Predictive value of circulating NMR metabolic biomarkers for type 2 diabetes risk in the UK Biobank study
Authors: Bragg Fiona , Trichia Eirini , Aguilar-Ramirez Diego , Bešević Jelena , Lewington Sarah , Emberson Jonathan
Published: May 2022

Background

Effective targeted prevention of type 2 diabetes (T2D) depends on accurate prediction of disease risk. We assessed the role of metabolomic profiling in improving T2D risk prediction beyond conventional risk factors.

Methods

Nuclear magnetic resonance (NMR) metabolomic profiling was undertaken on baseline plasma samples in 65,684 UK Biobank participants without diabetes and not taking lipid-lowering medication. Among a subset of 50,519 participants with data available on all relevant co-variates (sociodemographic characteristics, parental history of diabetes, lifestyle—including dietary—factors, anthropometric measures and fasting time), Cox regression yielded adjusted hazard ratios for the associations of 143 individual metabolic biomarkers (including lipids, lipoproteins, fatty acids, amino acids, ketone bodies and other low molecular weight metabolic biomarkers) and 11 metabolic biomarker principal components (PCs) (accounting for 90% of the total variance in individual biomarkers) with incident T2D. These 11 PCs were added to established models for T2D risk prediction among the full study population, and measures of risk discrimination (c-statistic) and reclassification (continuous net reclassification improvement [NRI], integrated discrimination index [IDI]) were assessed.

Results

During median 11.9 (IQR 11.1–12.6) years’ follow-up, after accounting for multiple testing, 90 metabolic biomarkers showed independent associations with T2D risk among 50,519 participants (1211 incident T2D cases) and 76 showed associations after additional adjustment for HbA1c (false discovery rate controlledp< 0.01). Overall, 8 metabolic biomarker PCs were independently associated with T2D. Among the full study population of 65,684 participants, of whom 1719 developed T2D, addition of PCs to an established risk prediction model, including age, sex, parental history of diabetes, body mass index and HbA1c, improved T2D risk prediction as assessed by the c-statistic (increased from 0.802 [95% CI 0.791–0.812] to 0.830 [0.822–0.841]), continuous NRI (0.44 [0.38–0.49]) and relative (15.0% [10.5–20.4%]) and absolute (1.5 [1.0–1.9]) IDI. More modest improvements were observed when metabolic biomarker PCs were added to a more comprehensive established T2D risk prediction model additionally including waist circumference, blood pressure and plasma lipid concentrations (c-statistic, 0.829 [0.819–0.838] to 0.837 [0.831–0.848]; continuous NRI, 0.22 [0.17–0.28]; relative IDI, 6.3% [4.1–9.8%]; absolute IDI, 0.7 [0.4–1.1]).

Conclusions

When added to conventional risk factors, circulating NMR-based metabolic biomarkers modestly enhanced T2D risk prediction.
Autonomic nervous system dysregulation in response to postural change in patients with pectus excavatum in Taiwan: a pilot study
Authors: Hsu Yu-Ting , Cheng Yeung-Leung , Chang Yi-Wei , Lan Chou-Chin , Wu Yao-Kuang , Yang Mei-Chen
Published: May 2022

Background

Pectus excavatum (PE) negatively impacts psychological function, but its effect on autonomic nervous system (ANS) function has not been investigated. We evaluated ANS function following postural changes in patients with PE.

Methods

The participants were 14 healthy men (control group) and 20 men with PE (study group). Psychological function was assessed using the visual analog scale for pain, Brief Symptom Rating Scale-5, and Beck Depression Inventory-II. Sleep quality was evaluated using the Pittsburgh Sleep Quality Index (PSQI). ANS regulation in response to postural change was measured in the supine position and immediately after sitting. All measurements were compared between the control and study groups at baseline and between the study groups before and after Nuss surgery.

Results

At baseline, upon postural change, symptomatic activity increased in the control group (50.3–67.4%, p = 0.035) but not in the study group (55.0–54.9%, p = 0.654); parasympathetic activity decreased in the control group (49.7–32.6%, p = 0.035) but not in the study group (45.1–45.1%, p = 0.654); and overall ANS regulation increased in the control group (1.02–2.08, p = 0.030) but not in the study group (1.22–1.22, p = 0.322). In response to postural change after Nuss surgery in the study group, sympathetic activity increased (48.7–70.2%, p = 0.005), parasympathetic activity decreased (51.3–29.8%, p = 0.005), and overall ANS regulation increased (0.95–2.36, p = 0.012).

Conclusion

ANS function in response to postural change is dysregulated in patients with PE, which improved after Nuss surgery.

Trial registrationClinicalTrials.gov, ID: NCT03346876, November 15, 2017, retrospectively registered,https://register.clinicaltrials.gov/prs/app/action/SelectProtocol?sid=S0007KGI&selectaction=Edit&uid=U0003JZU&ts=2&cx=cstxeg
Ginsenoside compound K inhibits the proliferation, migration and invasion of Eca109 cell via VEGF-A/Pi3k/Akt pathway
Authors: Huang Jianhou , Pan Dinglong , Liu Feng , Hong Yiting , Huang Gang , Huang Xiaowei , Wang Xinwen , Lin Zhiqiang
Published: May 2022

Objective

Esophageal cancer, one of the most common cancers in the upper digestive tract and is one of the leading cancer-related mortality worldwide. Accumulating studies found that Ginsenoside compound K (CK) has significantly anti-tumor effects, especially in the suppression of proliferation, migration, as well as invasion in various human cancers. While the effects of Ginsenoside CK in esophageal cancer have not been well studied. In our present study, we aim to explore the functions and mechanisms of Ginsenoside CK in the progression of esophageal cancer cells (Eca109).

Methods

Cell Counting Kit-8 (CCK-8), wound healing, transwell and flow cytometry assays were applied to analyze the effects of Ginsenoside CK in the progression of Eca109 cell, western blot assay was used to investigate the potential downstream signaling pathway after Ginsenoside CK treatment.

Results

Our study found that Ginsenoside CK can suppress cell proliferation, migration and invasion of Eca109 cell. Furthermore, the flow cytometry showed that Ginsenoside CK increased of apoptosis rates in Eca109 cell. The western blot results indicated that Ginsenoside CK decreased the expression of VEGF-A, P-Pi3k and P-Akt proteins. Moreover, the knockdown of VEGF-A gene could suppress cell proliferation, migration, invasion and induce apoptosis in Eca109 cell, and the expression of P-Pi3k and P-Akt proteins were significantly downregulated.

Conclusions

Our study suggests that Ginsenoside CK inhibits the proliferation, migration, invasion, and induced apoptosis of Eca109 cell by blocking VEGF-A/Pi3k/Akt signaling pathway.
Nanoengineering a metal–organic framework for osteosarcoma chemo-immunotherapy by modulating indoleamine-2,3-dioxygenase and myeloid-derived suppressor cells
Authors: Fan Qingxin , Zuo Jing , Tian Hailong , Huang Canhua , Nice Edouard C. , Shi Zheng , Kong Qingquan
Published: May 2022

Background

The high postoperative recurrence rate and refractoriness of relapsed tumors are still a conundrum for the clinical management of osteosarcoma (OS). New therapeutic options are urgently needed. Depriving the nourishment of myeloid-derived suppressor cells is a novel strategy to improve the immunosuppressive tumor microenvironment for enhanced OS therapy.

Methods

We synthesized a hyaluronic acid (HA)-modified metal–organic framework for combinational chemotherapy and immunotherapy of OS. Zeolitic Imidazolate Framework-8 (ZIF-8) was prepared by a one-pot synthetic method, Gemcitabine (Gem) and D-1-Methyltryptophan (D-1-MT) were loaded into the ZIF-8 during the synthesis process to make ZIF-8@Gem/D-1-MT nanoparticles (NPs). The end product (HA/ZIF-8@Gem/D-1-MT NPs) was obtained by HA modification on the surface of ZIF-8@Gem/D-1-MT NPs. The obtained HA/ZIF-8@Gem/D-1-MT NPs have excellent potential as a drug delivery vector for chemotherapy and immunotherapy in vitro and vivo.

Results

The results indicate that HA/ZIF-8@Gem/D-1-MT NPs were readily taken up by OS cells, and that the Gem and D-1-MT were effectively released into the acidic environment. The HA/ZIF-8@Gem/D-1-MT NPs could efficiently decrease OS cell viability (proliferation, apoptosis, cell cycle, migration and invasion). And HA/ZIF-8@Gem/D-1-MT NPs could reactivate antitumor immunity by inhibiting indoleamine 2,3 dioxygenase and myeloid-derived suppressor cells. Furthermore, animal experiments confirmed that HA/ZIF-8@Gem/D-1-MT NPs could induce intratumoral immune responses and inhibit tumor growth. Additionally, HA/ZIF-8@Gem/D-1-MT NPs have a good safety profile.

Conclusions

Our findings demonstrate that the combination of Gem with D-1-MT brings new hope for the improved treatment of OS, while the generation of the nanosystem has increased the application potential and flexibility of this strategy.
“Multidisciplinary management of post- infective osteoarthritis and secondary condylar resorption of temporomandibular joint: a case report in a 9 years-old female patient and a review of literature”
Authors: Festa Paola , Arezzo Elena , Vallogini Giulia , Vittucci Anna Chiara , Barbuti Domenico , Galeotti Angela
Published: May 2022

Background

Osteoarthritis and condylar resorption of temporomandibular joint (TMJ) has rarely been reported in children as consequence of otologic disease. We describe the management of a case in a 9-year-old female as long-term complication of an otomastoiditis and review the literature currently available on this topic.

Case presentation

A nine-years-old female patient referred to Emergency Room of Bambino Gesù Children’s Research Hospital, IRCCS (Rome,Italy) for an acute pain in the left preauricular area and reduced mandibular movements. In the medical history an otomastoiditis and periorbital cellulitis was reported at the age of six with complete remission of symptoms after antibiotic treatment. No recent history of facial trauma and no previous orthodontic treatment were reported. She was referred to a pediatric dentist that conducted a clinical examination according to the Diagnostic Criteria of Temporomandibular Disorders (DC/TMD) and was diagnosed with bilateral myalgia of the masticatory muscles and arthralgia at the level of the left TMJ. Then, a complete diagnostic path was performed that included multidisciplinary examinations by a rheumatologist, infectious disease specialist, ear nose and throat (ENT) doctor, a maxillofacial surgeon and a medical imaging specialist. Differential diagnosis included juvenile idiopathic arthritis, idiopathic condylar resorption, trauma, degenerative joint disease, neurological disease. Finally, unilateral post-infective osteoarthritis of the left TMJ with resorption of mandibular condyle was diagnosed. The patient went through a pharmacological therapy with paracetamol associated to counselling, jaw exercises and occlusal bite plate. After 1 month, the patient showed significant reduction of orofacial pain and functional recovery that was confirmed also one-year post-treatment. The novelty of this clinical case lies in the accurate description of the multidisciplinary approach with clinical examination, the differential diagnosis process and the management of TMD with conservative treatment in a growing patient.

Conclusions

Septic arthritis of temporomandibular joint and condylar resorption were described as complications of acute otitis media and/or otomastoiditis in children. We evidenced the importance of long-term follow-up in children with acute media otitis or otomastoiditis due to the onset of TMJ diseases. Furthermore, in the multidisciplinary management of orofacial pain the role of pediatric dentist is crucial for the diagnostic and therapeutic pathway to avoid serious impairment of mandibular function.
A behavior change wheel-based interactive pictorial health education program for hypertensive patients with low blood pressure health literacy: study protocol for a randomized controlled trial
Authors: Gan Wei , Zhang Qinghua , Yang Dan , Yin Jinyu , Wang Yujie , Song Li , Chen Ting , Qi Huan
Published: May 2022

Background

The prevalence of hypertension is increasing worldwide. Hypertension self-management usually involves the application and consideration of oral, written, or quantitative information. Hypertensive patients in China have limited high blood pressure health literacy (HBP-HL), which may lead to poorer clinical outcomes. This study aims to determine the feasibility and effectiveness of an interactive pictorial health education program based on behavior change wheel (BCW) theory and its effect on HBP-HL, self-efficacy, self-management ability, and health-related quality of life (HRQOL) in hypertensive patients with low HBP-HL.

Methods

This study is a randomized controlled trial (RCT). One of the municipal districts in Huzhou, China, will be randomly selected, and two communities with similar conditions within this district will be screened and selected. A total of 120 hypertensive patients aged 18 years and older will be recruited from these two community settings. One of the communities will be randomly allocated to an interactive pictorial health education program conducted by a comprehensive health literacy strategy that includes (i) training participants in effective health communication skills that address issues encountered in seeking medical care and (ii) the use of self-developed interactive pictorial hypertension education to improve patient understanding and behaviors versus a control group (routine community lecture health education only). The primary outcome measure is HBP-HL. Secondary outcomes are self-efficacy, self-management ability, HRQOL, social support, and improvement in blood pressure. Outcomes will be collected at 6, 9, and 12 months from trial entry.

Discussion

The strengths of this study are the establishment of a new health management program for hypertensive patients that closely combines BCW theory and health literacy. This trial has the potential to improve HBP-HL in hypertensive Chinese patients with low health literacy to improve the self-management of hypertension and help control blood pressure.

Trial registration

Clinical Trials.gov Protocol Registration and Results System ID NCT04327102. Prospectively registered on February 29, 2020
Community structure and insecticide resistance of malaria vectors in northern-central Myanmar
Authors: Zhong Daibin , Aung Pyae Linn , Mya Maung Maung , Wang Xiaoming , Qin Qian , Soe Myat Thu , Zhou Guofa , Kyaw Myat Phone , Sattabongkot Jetsumon , Cui Liwang , Yan Guiyun
Published: May 2022

Background

Myanmar is one of the six countries in the Greater Mekong Subregion (GMS) of Southeast Asia. Malaria vectors comprise many Anopheles species, which vary in abundance and importance in malaria transmission among different geographical locations in the GMS. Information about the species composition, abundance, and insecticide resistance status of vectorial systems in Myanmar is scarce, hindering our efforts to effectively control malaria vectors in this region.

Methods

During October and November 2019, larvae and adult females of Anopheles mosquitoes were collected in three sentinel villages of Banmauk township in northern Myanmar. Adult female mosquitoes collected by cow-baited tent collection (CBTC) and adults reared from field-collected larvae (RFCL) were used to determine mortality rates and knockdown resistance (kdr) against deltamethrin using the standard WHO susceptibility test. Molecular species identification was performed by multiplex PCR and ITS2 PCR, followed by DNA sequencing. The kdr mutation at position 1014 of the voltage-gated sodium channel gene was genotyped by DNA sequencing for all Anopheles species tested.

Results

A total of 1596 Anopheles mosquitoes from seven morphologically identified species groups were bioassayed. Confirmed resistance to deltamethrin was detected in the populations of An. barbirostris (s.l.), An. hyrcanus (s.l.), and An. vagus, while possible resistance was detected in An. annularis (s.l.), An. minimus, and An. tessellatus. Anopheles kochi was found susceptible to deltamethrin. Compared to adults collected by CBTC, female adults from RFCL had significantly lower mortality rates in the four species complexes. A total of 1638 individuals from 22 Anopheles species were molecularly identified, with the four most common species being An. dissidens (20.5%) of the Barbirostris group, An. peditaeniatus (19.4%) of the Hyrcanus group, An. aconitus (13.4%) of the Funestus group, and An. nivipes (11.5%) of the Annularis group. The kdr mutation L1014F was only detected in the homozygous state in two An. subpictus (s.l.) specimens and in a heterozygous state in one An. culicifacies (s.l.) specimen.

Conclusions

This study provides updated information about malaria vector species composition and insecticide resistance status in northern Myanmar. The confirmed deltamethrin resistance in multiple species groups constitutes a significant threat to malaria vector control. The lack or low frequency of target-site resistance mutations suggests that other mechanisms are involved in resistance. Continual monitoring of the insecticide resistance of malaria vectors is required for effective vector control and insecticide resistance management.

Graphical Abstract
Comparison of visceral fat lipolysis adaptation to high-intensity interval training in obesity-prone and obesity-resistant rats
Authors: Liu Yang , Li Yu , Cheng Baishuo , Feng Shige , Zhu Xiangui , Chen Wei , Zhang Haifeng
Published: May 2022

Background/objectives

Visceral obesity is one of the key features of metabolic syndrome. High-intensity interval training (HIIT) could effectively reduce visceral fat, but its effects show strong heterogeneity in populations with different degrees of obesity. The mechanism may be related to the differential adaptation to training between obesity phenotypes, namely obesity prone (OP) and obesity resistant (OR). The aim of the present study was to compare adaptive changes of visceral adipose lipolysis adaptation to HIIT between OP and OR animals and further explore the upstream pathway.

Methods

OP and OR Sprague Dawley rats were established after feeding a high-fat diet for 6 weeks; they were then divided into HIIT (H-OP and H-OR) and control (C-OP and C-OR) groups. After 12 weeks of HIIT or a sedentary lifestyle, animals were fasted for 12 h and then sacrificed for histology as well as gene and protein analysis. Visceral adipocytes were isolated without fasting for catecholamine stimulation and β3-adrenergic receptor (β3-AR) blockade in vitro to evaluate the role of upstream pathways.

Results

After training, there were no differences in weight loss or food intake between OP and OR rats (P > 0.05). However, the visceral fat mass, adipocyte volume, serum triglycerides and liver lipids of OP rats decreased by more than those of OR rats (P < 0.05). Meanwhile, the cell lipolytic capacity and the increase in the expression of β3-AR were higher in the OP compared with OR groups (P < 0.05). Although training did not increase sympathetic nervous system activity (P > 0.05), the cell sensitivity to catecholamine increased significantly in the OP compared with OR groups (P < 0.05). Following blocking β3-AR, the increased sensitivity disappeared.

Conclusion

With HIIT, OP rats lost more visceral fat than OR rats, which was related to stronger adaptive changes in lipolysis. Increased β3-AR expression mediated this adaptation.
Clinical and humanistic impact of pharmacotherapeutic follow-up in patients with type 1 diabetes mellitus treated judicially
Authors: Mendonça Thays S. , Oliveira William N. , Belo Vinícius S. , Silva Eduardo S. , Pereira Mariana L. , Obreli-Neto Paulo R. , Baldoni André O.
Published: May 2022

Background

There is a lack of studies that assess the effectiveness of pharmacotherapeutic follow-up in the context of the judicialization of insulin analogues.

Aims

To evaluate the clinical and humanistic impact of pharmacotherapeutic follow-up in patients with type 1 diabetes mellitus who receive insulin analogues by judicial decision in a Brazilian municipality.

Methods

A quasi-experimental study of the before-and-after type was carried out through pharmacotherapeutic follow-up. Patients who accepted to participate in the study underwent laboratory tests of glycemic and lipid profile before and after the intervention, and underwent five pharmaceutical consultations. In addition, quality of life and health, knowledge, and skills related to insulin application techniques were analyzed.

Results

28 patients participated in all stages. Of these, most were female (53.6%), with a mean age of 32.8 ± 11.6 years. After the intervention, there was a reduction in blood glucose levels, blood pressure, and increased body mass index. In addition, there was greater knowledge and skills regarding insulin application techniques, improved quality of life, health, greater number of medications used, reduction of pharmacotherapeutic problems, and improvement in eating habits.

Conclusion

The pharmacotherapeutic follow-up promoted clinical and humanistic benefits, with improvement in quality of life and health.
Efficacy and safety of umbilical cord-derived mesenchymal stem cells in Chinese adults with type 2 diabetes: a single-center, double-blinded, randomized, placebo-controlled phase II trial
Authors: Zang Li , Li Yijun , Hao Haojie , Liu Jiejie , Cheng Yu , Li Bing , Yin Yaqi , Zhang Qian , Gao Fei , Wang Haibin , Gu Shi , Li Jia , Lin Fengxiang , Zhu Yingfei , Tian Guanglei , Chen Yulong , Gu Weijun , Du Jin , Chen Kang , Guo Qinghua , Yang Guoqing , Pei Yu , Yan Wenhua , Wang Xianling , Meng Junhua , Zhang Saichun , Ba Jianming , Lyu Zhaohui , Dou Jingtao , Han Weidong , Mu Yiming
Published: May 2022

Background

To determine the efficacy and safety of umbilical cord-derived mesenchymal stem cells (UC-MSCs) in Chinese adults with type 2 diabetes mellitus (T2DM).

Methods

In this single-center, double-blinded, randomized, placebo-controlled phase II trial, 91 patients were randomly assigned to receive intravenous infusion of UC-MSCs (n = 45) or placebo (n = 46) three times with 4-week intervals and followed up for 48 weeks from October 2015 to December 2018. The primary endpoint was the percentage of patients with glycated hemoglobin (HbA1c) levels of < 7.0% and daily insulin reduction of ≥ 50% at 48 weeks. Additional endpoints were changes of metabolic control, islet β-cell function, insulin resistance, and safety.

Results

At 48 weeks, 20% of the patients in the UC-MSCs group and 4.55% in the placebo group reached the primary endpoint (p < 0.05, 95% confidence interval (CI) 2.25–28.66%). The percentage of insulin reduction of the UC-MSCs group was significantly higher than that of the placebo group (27.78% versus 15.62%, p < 0.05). The levels of HbA1c decreased 1.31% (9.02 ± 1.27% to 7.52 ± 1.07%, p < 0.01) in the UC-MSCs group, and only 0.63% in the placebo group (8.89 ± 1.11% to 8.19 ± 1.02%, p˃0.05; p = 0.0081 between both groups). The glucose infusion rate (GIR) increased significantly in the UC-MSCs group (from 3.12 to 4.76 mg/min/kg, p < 0.01), whereas no significant change was observed in the placebo group (from 3.26 to 3.60 mg/min/kg, p ˃ 0.05; p < 0.01 between both groups). There was no improvement in islet β-cell function in both groups. No major UC-MSCs transplantation-related adverse events occurred.

Conclusions

UC-MSCs transplantation could be a potential therapeutic approach for Chinese adults with T2DM.

Trial registration This study was registered on ClinicalTrials.gov (identifier: NCT02302599).
Exosomes and autophagy in ocular surface and retinal diseases: new insights into pathophysiology and treatment
Authors: Ma Shisi , Liu Xiao , Yin Jiayang , Hao Lili , Diao Yuyao , Zhong Jingxiang
Published: May 2022

Background

Ocular surface and retinal diseases are widespread problems that cannot be ignored in today’s society. However, existing prevention and treatment still have many shortcomings and limitations, and fail to effectively hinder the occurrence and development of them.

Main body

The purpose of this review is to give a detailed description of the potential mechanism of exosomes and autophagy. The eukaryotic endomembrane system refers to a range of membrane-bound organelles in the cytoplasm that are interconnected structurally and functionally, which regionalize and functionalize the cytoplasm to meet the needs of cells under different conditions. Exosomal biogenesis and autophagy are two important components of this system and are connected by lysosomal pathways. Exosomes are extracellular vesicles that contain multiple signaling molecules produced by multivesicular bodies derived from endosomes. Autophagy includes lysosome-dependent degradation and recycling pathways of cells or organelles. Recent studies have revealed that there is a common molecular mechanism between exosomes and autophagy, which have been, respectively, confirmed to involve in ocular surface and retinal diseases.

Conclusion

The relationship between exosomes and autophagy and is mostly focused on fundus diseases, while a deeper understanding of them will provide new directions for the pathological mechanism, diagnosis, and treatment of ocular surface and retinal diseases.
Sex differences in the aging murine urinary bladder and influence on the tumor immune microenvironment of a carcinogen-induced model of bladder cancer
Authors: Hamade Ali , Li Deyang , Tyryshkin Kathrin , Xu Minqi , Conseil Gwenaelle , Yolmo Priyanka , Hamilton Jake , Chenard Stephen , Robert Siemens D. , Koti Madhuri
Published: May 2022

Sex and age associated differences in the tumor immune microenvironment of non-muscle invasive bladder (NMIBC) cancer and associated clinical outcomes are emerging indicators of treatment outcomes. The incidence of urothelial carcinoma of the bladder is four times higher in males than females; however, females tend to present with a more aggressive disease, a poorer response to immunotherapy and suffer worse clinical outcomes. Recent findings have demonstrated sex differences in the tumor immune microenvironment of non-muscle invasive and muscle invasive bladder cancer and associated clinical outcomes. However, a significant gap in knowledge remains with respect to the current pre-clinical modeling approaches to more precisely recapitulate these differences towards improved therapeutic design. Given the similarities in mucosal immune physiology between humans and mice, we evaluated the sex and age-related immune alterations in healthy murine bladders. Bulk-RNA sequencing and multiplex immunofluorescence-based spatial immune profiling of healthy murine bladders from male and female mice of age groups spanning young to old showed a highly altered immune landscape that exhibited sex and age associated differences, particularly in the context of B cell mediated responses. Spatial profiling of healthy bladders, using markers specific to macrophages, T cells, B cells, activated dendritic cells, high endothelial venules, myeloid cells and the PD-L1 immune checkpoint showed sex and age associated differences. Bladders from healthy older female mice also showed a higher presence of tertiary lymphoid structures (TLSs) compared to both young female and male equivalents. Spatial immune profiling of N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN) carcinogen exposed male and female bladders from young and old mice revealed a similar frequency of TLS formation, sex differences in the bladder immune microenvironment and, age associated differences in latency of tumor induction. These findings support the incorporation of sex and age as factors in pre-clinical modeling of bladder cancer and will potentially advance the field of immunotherapeutic drug development to improve clinical outcomes.
Efficient 3D conformer generation of cyclic peptides formed by a disulfide bond
Authors: Tao Huanyu , Wu Qilong , Zhao Xuejun , Lin Peicong , Huang Sheng-You
Published: May 2022

Cyclic peptides formed by disulfide bonds have been one large group of common drug candidates in drug development. Structural information of a peptide is essential to understand its interaction with its target. However, due to the high flexibility of peptides, it is difficult to sample the near-native conformations of a peptide. Here, we have developed an extended version of our MODPEP approach, named MODPEP2.0, to fast generate the conformations of cyclic peptides formed by a disulfide bond. MODPEP2.0 builds the three-dimensional (3D) structures of a cyclic peptide from scratch by assembling amino acids one by one onto the cyclic fragment based on the constructed rotamer and cyclic backbone libraries. Being tested on a data set of 193 diverse cyclic peptides, MODPEP2.0 obtained a considerable advantage in both accuracy and computational efficiency, compared with other sampling algorithms including PEP-FOLD, ETKDG, and modified ETKDG (mETKDG). MODPEP2.0 achieved a high sampling accuracy with an average C$$\alpha$$
α
RMSD of 2.20 Å and 1.66 Å when 10 and 100 conformations were considered, respectively, compared with 3.41 Å and 2.62 Å for PEP-FOLD, 3.44 Å and 3.16 Å for ETKDG, 3.09 Å and 2.72 Å for mETKDG. MODPEP2.0 also reproduced experimental peptide structures for 81.35% of the test cases when an ensemble of 100 conformations were considered, compared with 54.95%, 37.50% and 50.00% for PEP-FOLD, ETKDG, and mETKDG. MODPEP2.0 is computationally efficient and can generate 100 peptide conformations in one second. MODPEP2.0 will be useful in sampling cyclic peptide structures and modeling related protein-peptide interactions, facilitating the development of cyclic peptide drugs.
Morphological disparity in extant and extinct sepiid phragmocones: morphological adaptions for phragmocone strength compared to those related to cameral liquid emptying hypotheses
Authors: Ward Peter D. , Veloso Job Lukas , Klug Christian
Published: May 2022

The phragmocone-bearing coleoid cephalopodsSepia,Sepiella,MetasepiaandHemisepius(sepiids) are the most diverse of all extant chambered cephalopods and show the highest disparity. As such, they have a great potential to serve as model organisms to better understand the paleobiology not only of extinct coleoids, but of extinct nautiloids and ammonoids as well. Here, we present new measurements from the phragmocones ofSepiaandSepiellaand relate these to known maximum depths. While these latter data remain few for some species, in aggregate they provide progress allowing this work. In so doing, we expand upon the great legacy of Sigurd von Boletzky. We show that deep water-inhabiting sepiids have phragmocones with a higher number of septa per length, a smaller area covered by the last chamber in relation to the volume of all previous phragmocone chambers, are smaller in size (length and volume), and bear dorsal shields that have strengthening central rib(s) compared to most species from shallower water; the very small endemic species of South Africa may be an exception. We show that the various subgenera defined by Khromov (1987) are not monophyletic clades but morphological groupings explicitly related to depth, partially evolved convergently. We conclude with analyses of Australian sepiid assemblages and show that these are depth related in ways analogous to ammonite and/or nautiloid assemblages of the past that are later commingled through post-mortal drift.
VHL Ser65 mutations enhance HIF2α signaling and promote epithelial-mesenchymal transition of renal cancer cells
Authors: Ma Xueyou , Tan Zenglai , Zhang Qin , Ma Kaifang , Xiao Jun , Wang Xiong , Wang Yanan , Zhong Mengjie , Wang Yu , Li Jing , Zeng Xing , Guan Wei , Wang Shaogang , Gong Kan , Wei Gong-Hong , Wang Zhihua
Published: May 2022

Background

Von Hippel-Lindau (VHL) disease is an autosomal dominant genetic neoplastic disorder caused by germline mutation or deletion of the VHL gene, characterized by the tendency to develop multisystem benign or malignant tumors. The mechanism of VHL mutants in pathogenicity is poorly understand.

Results

Here we identified heterozygous missense mutations c.193T > C and c.194C > G in VHL in several patients from two Chinese families. These mutations are predicted to cause Serine (c.193T > C) to Proline and Tryptophan (c.194C > G) substitution at residue 65 of VHL protein (p.Ser65Pro and Ser65Trp). Ser65 residue, located within the β-domain and nearby the interaction sites with hypoxia-inducing factor α (HIFα), is highly conserved among different species. We observed gain of functions in VHL mutations, thereby stabilizing HIF2α protein and reprograming HIF2α genome-wide target gene transcriptional programs. Further analysis of independent cohorts of patients with renal carcinoma revealed specific HIF2α gene expression signatures in the context of VHL Ser65Pro or Ser65Trp mutation, showing high correlations with hypoxia and epithelial-mesenchymal transition signaling activities and strong associations with poor prognosis.

Conclusions

Together, our findings highlight the crucial role of pVHL-HIF dysregulation in VHL disease and strengthen the clinical relevance and significance of the missense mutations of Ser65 residue in pVHL in the familial VHL disease.
A new subgradient extragradient method for solving the split modified system of variational inequality problems and fixed point problem
Authors: Sripattanet Anchalee , Kangtunyakarn Atid
Published: May 2022

We introduce a new subgradient extragradient algorithm utilizing the concept of the set of solutions of the split modified system of variational inequality problems (SMSVIP). Our main theorem is weak convergence theorem for such an algorithm for approximating the fixed point problem in a real Hilbert space. We also apply these results to approximate the split minimization problem. In the last section, we provide an example to illustrate the potential of our main theorem.
Existence and blow-up of weak solutions of a pseudo-parabolic equation with logarithmic nonlinearity
Authors: Lakshmipriya N. , Gnanavel S. , Balachandran K. , Ma Yong-Ki
Published: May 2022

In this paper, we prove the existence of weak solutions of a pseudo-parabolic equation with logarithmic nonlinearity in an interval $[0, T)$
[
0
,
T
)
by employing the Galerkin approximation method and compactness arguments. We show that the solutions become unbounded at a finite time $T^{\star}$

T
⋆

and find upper and lower bounds for this time.
Starchy and fibrous feedstuffs differ in their in vitro digestibility and fermentation characteristics and differently modulate gut microbiota of swine
Authors: Tiwari Utsav P. , Mandal Rabindra K. , Neupane Kabi Raj , Mishra Birendra , Jha Rajesh
Published: May 2022

Background

Alternative feedstuffs may contribute to reducing feed costs of pig production. But these feedstuffs are typically rich in fiber and resistant starch (RS). Dietary fibers and RS are fermented in the gastrointestinal tract (GIT) and modulate the microbial community. Certain microbes in the GIT can promote host health, depending on the type of fermentation substrates available. In this study, six alternative feedstuffs (three starchy: Okinawan sweet potato, OSP; yam, and taro, and three fibrous: wheat millrun, WMR; barley brewers grain, BBG; and macadamia nut cake, MNC) were evaluated for their in vitro digestibility and fermentation characteristics and their effects on pig’s hindgut microbial profile. After 2 steps of enzymatic digestion assay, residues were fermented using fresh pig feces as microbial inoculum, and gas production was recorded periodically for 72 h and modeled for fermentation kinetics. After fermentation, the residual liquid phase was analyzed for short-chain fatty acid (SCFA), and the solid phase was used to determine the nutrient’s digestibility and microbial community.

Results

In vitro ileal digestibility of dry matter and gross energy was higher in starchy than fibrous feedstuffs. Total gas and SCFA production were significantly higher (P < 0.001) in starchy feedstuffs than fibrous feedstuffs. Both acetate and propionate production was significantly higher (P < 0.001) in all starchy feedstuffs than BBG and MNC; WMR was in between. Overall alpha diversity was not significantly different within and between starchy and fibrous feedstuffs. Beta diversity (measured using bray Curtis dissimilarity distance) of starchy feedstuffs was significantly different (P < 0.005) than fibrous feedstuffs.

Conclusion

Starchy feedstuffs acted as a substrate to similar types of microbes, whereas fibrous feedstuffs resulted in a more diverse microbial population. Such alternative feedstuffs may exert comparable beneficial effects, thus may be included in swine diets to improve gut health.
A comprehensive model to predict severe acute graft-versus-host disease in acute leukemia patients after haploidentical hematopoietic stem cell transplantation
Authors: Shen Meng-Zhu , Hong Shen-Da , Lou Rui , Chen Rui-Ze , Zhang Xiao-Hui , Xu Lan-Ping , Wang Yu , Yan Chen-Hua , Chen Huan , Chen Yu-Hong , Han Wei , Wang Feng-Rong , Wang Jing-Zhi , Liu Kai-Yan , Huang Xiao-Jun , Mo Xiao-Dong
Published: May 2022

Background

Acute graft-versus-host disease (aGVHD) remains the major cause of early mortality after haploidentical related donor (HID) hematopoietic stem cell transplantation (HSCT). We aimed to establish a comprehensive model which could predict severe aGVHD after HID HSCT.

Methods

Consecutive 470 acute leukemia patients receiving HID HSCT according to the protocol registered at https://clinicaltrials.gov (NCT03756675) were enrolled, 70% of them (n = 335) were randomly selected as training cohort and the remains 30% (n = 135) were used as validation cohort.

Results

The equation was as follows: Probability (grade III–IV aGVHD) = $$\frac{1}{{1 + \exp \left( { - \,{\text{Y}}} \right)}}$$

1

1
+
exp

-

Y

, where Y = –0.0288 × (age) + 0.7965 × (gender) + 0.8371 × (CD3 + /CD14 + cells ratio in graft) + 0.5829 × (donor/recipient relation) − 0.0089 × (CD8 + cell counts in graft) − 2.9046. The threshold of probability was 0.057392 which helped separate patients into high- and low-risk groups. The 100-day cumulative incidence of grade III–IV aGVHD in the low- and high-risk groups was 4.1% (95% CI 1.9–6.3%) versus 12.8% (95% CI 7.4–18.2%) (P = 0.001), 3.2% (95% CI 1.2–5.1%) versus 10.6% (95% CI 4.7–16.5%) (P = 0.006), and 6.1% (95% CI 1.3–10.9%) versus 19.4% (95% CI 6.3–32.5%) (P = 0.017), respectively, in total, training, and validation cohort. The rates of grade III–IV skin and gut aGVHD in high-risk group were both significantly higher than those of low-risk group. This model could also predict grade II–IV and grade I–IV aGVHD.

Conclusions

We established a model which could predict the development of severe aGVHD in HID HSCT recipients.
The five tenets of family-based treatment for adolescent eating disorders
Authors: Rienecke Renee D. , Le Grange Daniel
Published: May 2022

Family-based treatment (FBT) is the leading treatment for adolescent eating disorders and is based on five tenets, or fundamental assumptions: (1) the therapist holds an agnostic view of the cause of the illness; (2) the therapist takes a non-authoritarian stance in treatment; (3) parents are empowered to bring about the recovery of their child; (4) the eating disorder is separated from the patient and externalized; and (5) FBT utilizes a pragmatic approach to treatment. Learning these tenets is crucial to the correct practice and implementation of manualized FBT. The purpose of the current paper is to provide an in-depth overview of these five tenets and to illustrate how they are used in clinical practice. This overview will aid clinicians who are learning FBT.