bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparison of the efficacy of Fractional Radiofrequency Microneedling alone and in combination with platelet‐rich plasma in neck rejuvenation: a clinical and optical coherence tomography study
Authors: Gawdat Heba , Allam Riham Samy Hanafy Mahmoud , Hegazy Rehab , Sameh Bassant , Ragab Nanis
Published: July 2021

Background

Esthetic improvement of the neck and cervicomental angle remains one of the most challenging aspects of rejuvenation. Fractional radiofrequency microneedling demonstrated significant skin tightening and lifting of lower third of the face.

Aim of work

To evaluate and compare fractional radiofrequency microneedling alone and in combination with autologous platelet‐rich plasma (PRP) in neck rejuvenation.

Methods

20 patients with mild to moderate neck laxity were randomized to receive 3 sessions of either fractional radiofrequency microneedling +PRP (group A) or fractional radiofrequency microneedling monotherapy (group B). Evaluation was done using optical coherence tomography to detect dermis thickness, measurement of cervicomental angle, a score done by two investigators blinded to used modality (GAIS) and patient satisfaction score.

Results

Both Groups showed a statistically significant improvement in all parameters. Comparing the two groups, the mean dermal thickness after treatment was higher in group A compared with B but was found statistically insignificant. More favorable results were reported in group A according to GAIS. Other parameters showed comparable results.

Conclusion

Fractional microneedle radiofrequency with insulated microneedles offers a safe and effective modality for mild to moderate neck laxity when used alone or in combination with PRP. It remains questionable whether combining fr‐RF microneedling with PRP provides more favorable results in terms of efficacy and side effects.
Investigation on factors related to uterine fibroids in rural women of northern Anhui province
Authors: Wu Bing‐Jie , Wei Wu , Hu Cheng‐Yang , Zhang Xiu‐Jun , Zhong Fei
Published: July 2021

Aim

Given the increasing prevalence of hysteromyoma among the Chinese rural women of childbearing age, it is imperative that more attention should be given to researching risk factors that predispose women to this condition so that early preventive measures may be taken. Our study investigates potential risk factors for uterine fibroids such as participants' demographic characteristics (age, ethnicity, education), physiological characteristics (age at menarche, primiparous age), and the occurrence of several different female reproductive diseases (vaginitis, pelvic inflammatory disease).

Methods

2200 rural women of reproductive age were screened from a cross‐sectional study carried out in the northern Anhui province. Data were collected by questionnaire surveys, gynecological and laboratory examinations and were subjected to univariate and multivariate analysis to evaluate the risk factors for uterine fibroids.

Results

Of the 2200 women, 440 had uterine fibroids. In general, women with endometriosis, ovarian cysts and early menarche were more likely to suffer from hysteromyoma. Factors including higher parity, late age of first childbirth, and a regular menstrual cycle were associated with the reduced risk of uterine fibroids.

Conclusions

Our findings indicate that parameters such as earlier age of menarche, early primiparous age, lower parity and a variety of female reproductive diseases were associated with an increased risk of uterine fibroids. These findings may be used to guide the formulation of effective prevention and intervention protocols to improve the reproductive health of rural women.
A new approach to schooling in a diverse society: A research fable
Authors: Steele Claude M.
Published: July 2021

The pioneer of both stereotype threat and self‐affirmation theory, Claude Steele, provides the concluding piece to the special issue, reflecting on the interplay between theoretical and applied questions raised by this body of research and the contributions—past, present, and potential—of self‐affirmation theory to understanding the societal issue of educational disparities.
Melatonin inhibits lung cancer development by reversing the Warburg effect via stimulating the SIRT3/PDH axis
Authors: Chen Xiangyun , Hao Bingjie , Li Dan , Reiter Russel J. , Bai Yidong , Abay Baigenzhin , Chen Guojie , Lin Shumeng , Zheng Tiansheng , Ren Yanbei , Xu Xiao , Li Ming , Fan Lihong
Published: July 2021

Recently, the morbidity and mortality from lung cancer have continued to increase. Mitochondrial dysfunction plays a key role in apoptosis, proliferation, and the bioenergetic reprogramming of cancer cells, especially for energy metabolism. Herein, we investigated the ability of melatonin (MLT) to influence lung cancer growth and explored the association between mitochondrial functions and the progression of lung tumors. The deacetylase, sirtuin 3 (Sirt3), is a pivotal player in maintenance of mitochondrial function, among participating in ATP production by regulating the acetylone and pyruvate dehydrogenase complex (PDH). We initially found that MLT inhibited lung cancer growth in the Lewis mouse model. Similarly, we observed that MLT inhibited the proliferation of lung cancer cells (A549, PC9, and LLC cells), and the underlying mechanism of MLT was related to reprogramming cancer cell metabolism, accompanied by a shift from cytosolic aerobic glycolysis to oxidative phosphorylation (OXPHOS). These changes were accompanied by higher ATP production, an elevated ATP production‐coupled oxygen consumption rate (QCR), higher ROS levels, higher mito‐ROS levels, and lower lactic acid secretion. Additionally, we observed that MLT improved mitochondrial membrane potential and the activities of complexes Ⅰ and Ⅳ in the electron transport chain. Importantly, we also found and verified that the foregoing changes resulted from activation of Sirt3 and PDH. As a result of these changes, MLT significantly enhanced mitochondrial energy metabolism to reverse the Warburg effect via increasing PDH activity with stimulation of Sirt3. Collectively, these findings suggest the potential use of melatonin as an anti‐lung cancer therapy and provide a mechanistic basis for this proposal.
THE POZO MORO RELIEFS (CHINCHILLA, SPAIN): A MEDITERRANEAN HERO BETWEEN EAST AND WEST
Authors: García Cardiel Jorge , Olmos Romera Ricardo
Published: July 2021

At Pozo Moro, archaeologists discovered the oldest series of architectural and sculptural remains currently known in Iberian culture. It is traditionally assumed that they were part of a single ten‐meters‐high tower that was built – and immediately collapsed – in the late sixth century BC, some fifty years before an Iberian necropolis flourished around its ruins. This paper proposes that the site housed not just one, but various monuments, built at different times, that depicted the deeds of a local version of a Mediterranean hero, an ‘Iberian Heracles’ whose saga was to some extent known throughout the Mediterranean and used everywhere to bolster local claims to power.
Urbanization Is No Longer Driven by Migration in Low‐ and Middle‐Income Countries (1985–2015)
Authors: Menashe‐Oren Ashira , Bocquier Philippe
Published: July 2021

Across the world, populations have transitioned to inhabiting urban spaces, and in low‐ and middle‐income countries the proportion of people living in cities is expected to continue to increase. Anticipation of this fundamental process calls for a better understanding of the demographic factors that drive the urban transition. By indirectly estimating the joint contribution of migration and administrative reclassification to urban transition in 129 countries using urban and rural population by age and sex data available from the United Nations over 1985–2015, we find that differences in natural increase between the rural and urban sectors explain most of the urbanization over the 30‐year period examined. Over the urban transition, the role of migration and reclassification declines and becomes negligible. Despite data limitations, we confirm that it is misleading to view migration as fueling urbanization in low‐ and middle‐income countries.
Publication misrepresentation among pediatric anesthesiology fellowship applicants: A retrospective single‐center cohort study
Authors: Mehta Ashin , Patel Palak , Caruso Thomas J. , Anderson Thomas Anthony
Published: July 2021

Background

Many medical specialties have found publication misrepresentation in residency and fellowship applications, but pediatric anesthesia fellowship application data is lacking.

Aims

We sought to determine the prevalence of publication misrepresentation among pediatric anesthesia fellowship applications.

Methods

In this retrospective cohort study, fellowship applications to Stanford University's pediatric anesthesiology fellowship program from 2009 to 2019 were reviewed. Only peer‐reviewed journal articles listed as accepted or published were included. Nine additional variables were collected: applicant age, gender, citizenship status, American vs. international medical school, public vs. private medical school, allopathic doctor versus osteopathic doctor, number of years between college and medical school, additional degrees, and application year. The primary outcome was the rate of publication misrepresentation, defined as peer‐reviewed journal citations listed on the application that could not be verified or on which the applicant was not listed as an author. Secondary outcomes were the associations between publication misrepresentation and the additional collected variables.

Results

1280 peer‐reviewed journal publications from 877 applicants were reviewed. 3.4% of all citations listed as peer‐reviewed journal articles were misrepresented and 9.0% of all applicants with at least 1 publication had ≥1 misrepresented publications. 30.2% of publications labelled “misrepresented” were located in our search of databases but did not have the applicant as an author, and 69.8% could not be located using the search databases. Only one of the 9 collected variables (public vs private medical school) was significantly associated with publication misrepresentation.

Conclusions

In this single‐center retrospective study, publication misrepresentation was found to occur in one out of 11 pediatric anesthesia fellowship applications with at least one publication. Since residency and fellowship applicant publications may be heavily weighted during the application process, programs may want to include additional inquiries into the accuracy of applicant publications.
‘Youth of the world, unite so that you may live’: Youth, internationalism, and the Popular Front in the World Youth Congress Movement, 1936–1939
Authors: Lavery Kevin P.
Published: July 2021

During the Popular Front era (1934–1939), communists and liberals participated in new arenas of ideological contact through civil society. Among these was the World Youth Congress Movement (WYCM), an organization that embodied the convergence of three powerful forces of the 1930s: youth, internationalism, and the Popular Front. Although liberal internationalists initiated the WYCM, the involvement of communists drew criticism from socialists, conservatives, and fascists. While historians have traditionally described it as a communist front, the WYCM deserves reconsideration in light of new understandings of youth activism in the 1930s. In tracing the evolution of the movement, this study illustrates how the WYCM served as a space in which liberals and communists coordinated and competed to mobilize youth in the struggle for peace and cooperation. In youth, these groups found a shared interest that allowed them to paper over their contradictions, but only as long as their higher‐order interests aligned.
Alagille syndrome: Oral manifestations—A case report
Authors: Anacleto Murilo Augusto , Melo Christiane Fernandes Ribeiro , Oliveira Rafaela Peixoto , da Silva Luís Candido Pinto , Taitson Paulo Franco
Published: July 2021

The Alagille syndrome (AGLS) is a rare condition, with few studies reported in the literature, especially in the field of dentistry. It consists of a disease involving many systemic problems and specific facial features. The liver and heart are the most intensely affected organs, and depending on the severity, it may be necessary to perform transplants. It is an autosomal dominant disease with a variable expressivity, and its prevalence is 1/100,000 live births. Dental findings are conflicting. Some authors claim that dental anomalies occur only in deciduous dentitions; however, there is evidence that permanent teeth can also be affected, as will be described in this paper, through a case report of a patient diagnosed with AGLS, who sought out the Dentistry service at Pontifical Catholic University of Minas Gerais, complaining of a strong stain in her teeth, severe dental crowding, and a facial appearance of prognathism.
A high‐need, high‐impact educational session on firearms and death by suicide
Authors: Bryan Jennifer L. , Chen Rebecca L. , Moon Andrew , Asghar‐Ali Ali A.
Published: July 2021

Background

The suicide rate among Veterans is 1.5 times greater than that for civilians, partly a result of the high use of firearms as the means for suicide. One effective strategy to reduce Veteran suicide by firearms is to provide counseling on firearm safety as a method of means reduction. However, many clinicians do not discuss firearm safety with Veterans.

Aims

This study evaluates a one‐hour educational seminar for clinicians on lethal means safety.

Materials and Methods

One hundred and ninety clinicians from the Veterans Health Administration, including social workers, psychologists, psychiatrists, and nurses, participated in the training. The seminar was streamed during the South Central Mental Health Illness Research, Education and Clinical Center's Community‐Based Outpatient Clinic Mental Health Grand Rounds, for which participants were eligible for continuing education units. Data were collected immediately after the training and four months later.

Results

After completing the training, participants believed that it was important to speak with Veterans about firearm safety and felt knowledgeable and empowered to do so. Four months after the seminar, participants had counseled, on average, over half of Veterans treated about lethal means safety.

Discussion

Participants reported the value of normalizing discussions about firearm safety with their Veterans and focusing on the safety aspect while discussing firearms.

Conclusions

This webinar was effective in providing clinicians the skills to talk with Veterans about firearm safety and continued to impact their practice four months after training. The training is available for free on our website at https://www.mirecc.va.gov/visn16/public‐health‐approach‐to‐firearms‐and‐death‐by‐suicide.asp.
Identification of a novel HLA‐A*24 allele, A*24:537, identified in three individuals in an Indian family
Authors: D'Silva Selma Z. , Phuntsok Tenzin , Tambe Manisha , Rajak Jyoti , Singh Meenakshi
Published: July 2021

The novel HLA‐A*24:537 allele differs from HLA‐A*24:02:01:01 by a nucleotide change at gDNA 294 C → T.
Blood transfusions in gunshot‐wound‐related emergency department visits and hospitalizations in the United States
Authors: Goel Ruchika , Zhu Xianming , Makhani Sarah , Petersen Molly R. , Josephson Cassandra D. , Katz Louis M. , Shaz Beth H. , Austin Richard , Crowe Elizabeth P. , Ness Paul M. , Gehrie Eric A. , Frank Steven M. , Bloch Evan M. , Tobian Aaron A. R.
Published: July 2021

Background

The United States (US) leads all high‐income countries in gunshot wound (GSW) deaths. However, previous US studies have not evaluated the national blood transfusion utilization patterns in hospitalized GSW patients.

Methods

Data from 2016 to 2017 were analyzed from the Nationwide Emergency Department Sample (NEDS) and Nationwide Inpatient Sample (NIS), the largest all‐payer emergency department (ED) and inpatient databases, respectively. Using stratified probability sampling, weights were applied to generate nationally representative estimates. Multivariable Poisson‐regression models were used to estimate prevalence ratios (PR) of blood transfusion.

Results

There were 168,315 ED visits and 58,815 hospitalizations (age = 18–90 years) following a GSW. The majority of hospitalizations were men (88.5%), age 18–24 years (31.8%), and assault‐related GSW (51.3%). Blacks had the largest proportion (48.7%) overall of all GSW hospitalizations; Whites accounted for the highest proportion of intentional self‐harm injuries (72.4%). Blood transfusions occurred in 12.7% of hospitalizations (12.0% red blood cell [RBC], 4.9% plasma, and 2.5% platelet transfusions). Only 1.9% of cases were associated with transfusion of all three blood components. Hospitalizations with major/extreme severity of illness had significantly higher prevalence of transfusion versus those with mild/moderate severity [crude PR = 4.79 (95%CI:4.15–5.33, p < .001)]. Overall, 8.2% of hospitalizations with GSW died, of whom 26.8% required blood transfusions, which was significantly higher than survivors [crude PR = 2.34 (95%CI:2.10–2.61, p < .001)]. The vast majority (95%) of the transfusions among those who died were within 48 h since admission.

Conclusions

Gun‐related violence is a public health emergency in the US, and GSWs are a source of significant mortality, blood utilization, and health care costs.
Equine inflammatory response to abdominal surgery in the absence of gastrointestinal disease
Authors: Bowlby Charles , Mudge Margaret , Schroeder Eric , Godman Jennifer , Hurcombe Samuel
Published: July 2021

Objective

To investigate the, equine inflammatory response to ventral midline celiotomy in the absence of gastrointestinal disease in horses of varying body condition scores primarily using serial measurements of serum amyloid A (SAA).

Design

Experimental clinical study.

Setting

University teaching hospital.

Animals

Ten adult light breed horses free of any clinical disease, 5 with body condition score (BCS) 3–4/9 and 5 with BCS 7–8/9.

Interventions

Horses had a ventral midline celiotomy performed under general anesthesia, including manual decompression of the small intestine. SAA, semiquantitative fibrinogen, plasma lactate, and WBC count were measured in the blood preoperatively and at 12, 24, 48, 72, 120, and 168 hours postoperatively. Complete serum biochemistry was performed preoperatively and 24 and 72 hours postoperatively. Serial abdominocentesis was also performed with peritoneal fluid analysis of SAA, total protein, lactate, WBC count, and cytology.

Measurements and main results

Significant (P < 0.05) increases in serum SAA were noted at 12, 24, and 48 hours postoperatively (124.6 ± 68.6, 390.8 ± 209.0, 568.6 ± 197.7 μg/mL), and most horses had values approaching normal at 168 hours postoperatively (174.4 ± 307.7 μg/mL). Other values such as fibrinogen also increased in response to surgery but did not return to normal within the measured time points. Horses with high BCS did not have significantly different serum SAA compared to horses with low BCS. Peritoneal fluid SAA did not increase significantly at 12 hours postoperatively.

Conclusions

The information from this study can be used to help determine the effect of anesthesia and surgical intestinal manipulation resulting in increased SAA when a comparison to clinical or experimental cases is needed.
Perforations of tri‐layer nitrile‐latex and natural rubber latex gloves during ex‐vivo equine intestinal anastomoses
Authors: Averay Kate , Ward Michael , Verwilghen Denis
Published: July 2021

Objective

To compare perforation rates between tri‐layer nitrile‐latex and natural rubber latex surgical gloves after single‐layer end‐to‐end jejunojejunal anastomoses in equine cadavers.

Study Design

Prospective randomized ex‐vivo study.

Sample Population

Pairs of surgical gloves (n = 46) worn during jejunojejunal anastomoses.

Methods

Tri‐layer nitrile‐latex and rubber latex pairs of gloves were equally but randomly allocated to a right‐handed surgeon performing 46 single‐layer end‐to‐end jejunojejunal anastomoses on cadaveric material. Number and location of perforations were determined with the water leak test after each procedure. Ten unused pairs of both glove types were tested as controls.

Results

At least one perforation occurred in 41% (19/46) of the pairs of gloves. Glove perforations were present in 22% (5/23; 95% CI: 9–42) of tri‐layer glove pairs and 61% (14/23; 95% CI: 41–78) of the rubber glove pairs. The odds of glove perforation were 5.6 times (p = .009, 95% CI: 1.5–20.5) lower when tri‐layer rather than rubber gloves were used. The duration of procedure did not affect the risk of glove perforation (p = .679). No perforations were observed in the unused gloves.

Conclusion

Perforations were less common when the surgeon wore tri‐layer nitrile‐latex gloves rather than to the natural rubber latex gloves tested in this study.

Clinical Relevance

Tri‐layer nitrile‐latex gloves were more resistant to perforations in experimental settings; further studies may confirm that they are also superior in a clinical setting.
Study of artificial water replenishment for wetland restoration
Authors: Liu Jianwei , Zhang Qiang , Wang Zhipeng , Yang Bing , Li Yao
Published: July 2021

The degradation of wetlands has caused regional environment and climate problems in the Sanjiang Plain. To provide a reference for wetland protection and restoration, two artificial water replenishment schemes were designed and four indicators—water quantity, ammonia nitrogen, total nitrogen and total phosphorus—were chosen to analyse results simulated by an environmental fluid dynamics code model. Simulation results showed that the wetlands receive a suitable amount of water and reach a normal water elevation, and the concentration of most water quality indicators decreased. In addition, a fuzzy analytic hierarchy process was used to select the four indicators and 30 different combinations were designed. Following the fuzzy calculation, the comprehensive scores of 29 combinations showed that a scheme involving multiple replenishments is better than a scheme of a single replenishment. This study indicates that an effective method for restoring wetlands near or surrounding irrigation areas is rational allocation of water resources.
Una propuesta innovadora para la enseñanza del abordaje del delito sexual en el pregrado de la carrera de Medicina
Authors: Olaya Contreras Mercedes , Franco Zuluaga Jorge Andrés , Zapata Monsalve Brunilda del Socorro
Published: July 2021

El delito sexual sigue siendo una problemática frecuente en nuestro medio. Los médicos de todos los niveles de atención deben estar preparados para la mejor atención a las víctimas y además para la recolección del material probatorio requerido por la justicia. Se expone el planteamiento y desarrollo del “Taller de delito sexual” como experiencia pedagógica para estudiantes de medicina dentro de su cátedra de Medicina Legal.
Mecanismos fisiopatológicos relacionados con la infección por SARS-CoV-2 en las personas expuestas durante 2019 y 2020.
Authors: Escobar Domingo María José , Escobar Domingo Daniela Paola , Moreno Correa Sandra
Published: July 2021

La presente revisión describe los mecanismos fisiopatológicos relacionados con la infección por el Coronavirus de 2019, (COVID-19 ó SARS-CoV-2). Este virus descubierto en  Wuhan-China, presentó una transmisión zoonótica y posteriormente se transmitió entre humanos a través de aerosoles y superficies contaminadas con un índice alto de contagio desatando una Pandemia. A través de búsqueda sistemática en MEDLINE Y EMBASE, se seleccionaron los estudios que apuntan al objetivo general. Se discute sobre el genoma, estructura, receptor celular, respuesta inmune y diseminación hacia otros tejidos. En conclusión, el virus analizado, presenta factores que inciden en la severidad de la manifestación clínica y en la predisposición de adultos mayores y/o con comorbilidades, a presentar fenómenos inflamatorios generalizados. La expresión del receptor celular es un factor importante en la progresión. Aunque existe evidencia de la presencia viral en SNC, se requieren estudios que profundicen la acción del virus sobre este y otros tejidos.
Adhesion dynamics in the neocortex determine the start of migration and the post-migratory orientation of neurons
Authors: Epifanova Ekaterina , Salina Valentina , Lajkó Denis , Textoris-Taube Kathrin , Naumann Thomas , Bormuth Olga , Bormuth Ingo , Horan Stephen , Schaub Theres , Borisova Ekaterina , Ambrozkiewicz Mateusz C. , Tarabykin Victor , Rosário Marta
Published: July 2021

Zeb2 controls neocortex structure by regulating migration onset and neuronal orientation via Nrp1 and Cdh6 adhesive pathways.
COUP-TFI specifies the medial entorhinal cortex identity and induces differential cell adhesion to determine the integrity of its boundary with neocortex
Authors: Feng Jia , Hsu Wen-Hsin , Patterson Denis , Tseng Ching-San , Hsing Hsiang-Wei , Zhuang Zi-Hui , Huang Yi-Ting , Faedo Andrea , Rubenstein John L. , Touboul Jonathan , Chou Shen-Ju
Published: July 2021

Cortical regions are determined by patterning transcription factors and segregated by differential cell affinity.
Restructuring of the plasma membrane upon damage by LC3-associated macropinocytosis
Authors: Sønder Stine Lauritzen , Häger Swantje Christin , Heitmann Anne Sofie Busk , Frankel Lisa B. , Dias Catarina , Simonsen Adam Cohen , Nylandsted Jesper
Published: July 2021

Plasma membrane regeneration after injury requires the removal of damaged membrane via LC3-associated macropinocytosis.
Unique knowledge, unique skills, unique role: Aboriginal and Torres Strait Islander Health Workers in Queensland, Australia
Authors: Topp Stephanie M , Tully Josslyn , Cummins Rachel , Graham Veronica , Yashadhana Aryati , Elliott Lana , Taylor Sean
Published: July 2021

Aboriginal and Torres Strait Islander Health Workers (A&TSIHWs) are a professional cadre of Australian health workers typically located in primary care clinics. The role is one of only two that is ‘identified’— that is, it must be occupied by an Aboriginal and/or Torres Strait Islander person — and holds specific responsibilities in relation to advocating for facility-level cultural safety. However, lack of understanding of the distinctive skills, scope and value associated with the A&TSIHW role remains pervasive in the broader health workforce. Positioned to represent the perspective of those working as A&TSIHWs, and drawing on 83 in-depth interviews with A&TSIHWs and others, this qualitative study reports on the core functions and distinctive orientation of the role, and seeks to articulate its distinctive value in the modern Queensland health service. Findings highlight the multifaceted (generalist) nature of the A&TSIHW role, which comprises three core functions: health promotion, clinical service and cultural brokerage. Underpinning these cross-cutting functions, is the role’s unique orientation, defined by client-centredness and realised through Indigenous strengths based ways of knowing, being and doing. The findings highlight how the A&TSIHW role is one of the only mechanisms through which Aboriginal and Torres Strait Islander knowledge can be brought to bear on context-specific adaptations to routine health service practices; and through which the impacts of lack of cultural or self-awareness among some non-Indigenous health professionals can be mitigated. The complexity of such work in a government health system where a dominant biomedical culture defines what is valued and therefore resourced, is under-recognised and undervalued and contributes to pressures and stress that are potentially threatening the role's long-term viability.
Fruit and vegetable consumption and the risk of type 2 diabetes: a systematic review and dose–response meta-analysis of prospective studies
Authors: Halvorsen Rine Elise , Elvestad Mathilde , Molin Marianne , Aune Dagfinn
Published: July 2021

Background

The association between intake of fruit and vegetables and their subtypes, and the risk of type 2 diabetes has been investigated in several studies, but the results have been inconsistent.

Objective

We conducted an updated systematic review and dose–response meta-analysis of prospective studies on intakes of fruit and vegetables and fruit and vegetable subtypes and the risk of type 2 diabetes.

Design

PubMed and Embase databases were searched up to 20 October 2020. Prospective cohort studies of fruit and vegetable consumption and type 2 diabetes mellitus were included. Summary relative risks (RRs) and 95% CIs were estimated using a random effects model.

Results

We included 23 cohort studies. The summary RR for high versus low intake and per 200 g/day were 0.93 (95% CI: 0.89 to 0.98, I2=0%, n=10 studies) and 0.98 (95% CI: 0.95 to 1.01, I2=37.8%, n=7) for fruit and vegetables combined, 0.93 (95% CI: 0.90 to 0.97, I2=9.3%, n=20) and 0.96 (95% CI: 0.92 to 1.00, I2=68.4%, n=19) for fruits and 0.95 (95% CI: 0.88 to 1.02, I2=60.4%, n=17) and 0.97 (95% CI: 0.94 to 1.01, I2=39.2%, n=16) for vegetables, respectively. Inverse associations were observed for apples, apples and pears, blueberries, grapefruit and grapes and raisins, while positive associations were observed for intakes of cantaloupe, fruit drinks, fruit juice, brussels sprouts, cauliflower and potatoes, however, most of these associations were based on few studies and need further investigation in additional studies.

Conclusions

This meta-analysis found a weak inverse association between fruit and vegetable intake and type 2 diabetes risk. There is indication of both inverse and positive associations between intake of several fruit and vegetables subtypes and type 2 diabetes risk, however, further studies are needed before firm conclusions can be made.
Unintended consequences: quantifying the benefits, iatrogenic harms and downstream cascade costs of musculoskeletal MRI in UK primary care
Authors: Sajid Imran Mohammed , Parkunan Anand , Frost Kathleen
Published: July 2021

Objectives

The largest proportion of general practitioner (GP) magnetic resonance imaging (MRI) is musculoskeletal (MSK), with consistent annual growth. With limited supporting evidence and potential harms from early imaging overuse, we evaluated practice to improve pathways and patient safety.

Methods

Cohort evaluation of routinely collected diagnostic and general practice data across a UK metropolitan primary care population. We reviewed patient characteristics, results and healthcare utilisation.

Results

Of 306 MSK-MRIs requested by 107 clinicians across 29 practices, only 4.9% (95% CI ±2.4%) appeared clearly indicated and only 16.0% (95% CI ±4.1%) received appropriate prior therapy. 37.0% (95% CI ±5.5%) documented patient imaging request. Most had chronic symptoms and half had psychosocial flags. Mental health was addressed in only 11.8% (95% CI ±6.3%) of chronic sufferers with psychiatric illness, suggesting a solely pathoanatomical approach to MSK care. Only 7.8% (95% CI ±3.0%) of all patients were appropriately managed without additional referral. 1.3% (95% CI ±1.3%) of scans revealed diagnoses leading to change in treatment (therapeutic yield). Most imaged patients received pathoanatomical explanations to their symptoms, often based on expected age or activity-related changes. Only 16.7% (95% CI ±4.2%) of results appeared correctly interpreted by GPs, with spurious overperception of surgical targets in 65.4% (95% CI ±5.3%) who suffered ‘low-value’ (ineffective, harmful or wasteful) post-MRI referral cascades due to misdiagnosis and overdiagnosis. Typically, 20%–30% of GP specialist referrals convert to a procedure, whereas MRI-triggered referrals showed near-zero conversion rate. Imaged patients experienced considerable delay to appropriate care. Cascade costs exceeded direct-MRI costs and GP-MSK-MRI potentially more than doubles expenditure compared with physiotherapist-led assessment services, for little-to-no added therapeutic yield, unjustifiable by cost–consequence or cost–utility analysis.

Conclusion

Unfettered GP-MSK-MRI use has reached unaccceptable indication creep and disutility. Considerable avoidable harm occurs through ubiquitous misinterpretation and salient low-value referral cascades for two-thirds of imaged patients, for almost no change in treatment. Any marginally earlier procedural intervention for a tiny fraction of patients is eclipsed by negative consequences for the vast majority. Only 1–2 patients need to be scanned for one to suffer mismanagement. Direct-access imaging is neither clinically, nor cost-effective and deimplementation could be considered in this setting. GP-MSK-MRI fuels unnecessary healthcare utilisation, generating nocebic patient beliefs and expectations, whilst appropriate care is delayed and a high burden of psychosocial barriers to recovery appear neglected.
Prognosis palliative care study, palliative prognostic index, palliative prognostic score and objective prognostic score in advanced cancer: a prospective comparison
Authors: Lee Seung Hun , Lee Jeong Gyu , Choi Young Jin , Seol Young Mi , Kim Hyojeong , Kim Yun Jin , Yi Yu Hyeon , Tak Young Jin , Kim Gyu Lee , Ra Young Jin , Lee Sang Yeoup , Cho Young Hye , Park Eun Ju , Lee Youngin , Choi Jungin , Lee Sae Rom , Kwon Ryuk Jun , Son Soo Min
Published: July 2021

Background

Predicting how long a patient with far advanced cancer has to live is a significant part of hospice and palliative care. Various prognostic models have been developed, but have not been fully compared in South Korea.

Objectives

We aimed to compare the accuracy of the Prognosis in Palliative Care Study (PiPS), Palliative Prognostic Index (PPI), Palliative Prognostic Score (PaP) and Objective Prognostic Score (OPS) for patients with far advanced cancer in a palliative care unit in South Korea.

Methods

This prospective study included patients with far advanced cancer who were admitted to a single palliative care unit at the National University Hospital. Variables for calculating the prognostic models were recorded by a palliative care physician. The survival rate was estimated using the Kaplan-Meier method. The sensitivity, specificity, positive predictive value and negative predictive value of each model were calculated.

Results

A total of 160 patients participated. There was a significant difference in survival rates across all groups, each categorised through the five prognostic models. The overall accuracy (OA) of the prognostic models ranged between 54.5% and 77.6%. The OA of clinicians’ predictions of survival ranged between 61.9% and 81.3%.

Conclusion

The PiPS, PPI, PaP and OPS were successfully validated in a palliative care unit of South Korea. There was no difference in accuracy between the prognostic models, and OA tended to be lower than in previous studies.
Virtual reality in hospice: improved patient well-being
Authors: Lloyd Anna , Haraldsdottir Erna
Published: July 2021

Background

Virtual reality (VR) technology as a therapeutic intervention has been gaining attention in healthcare settings in recent years. Studies suggest that using the technology can help alleviate symptoms such as pain and anxiety and induce positive emotions for people in hospital. Managing symptoms and promoting emotional and psychological well-being are core palliative care goals of relieving suffering of people with life-limiting illness. Accordingly, VR may be highly beneficial for use in hospice care yet remains underdeveloped in such settings. This qualitative study aimed to trial the technology and consider what benefits may emerge for hospice in patients.

Methods

A one-off VR session was offered to patients at a hospice in Scotland. Sessions were observed by a researcher and followed by qualitative semi-structured interviews to discuss the experience with those who took part. Interviews were audio recorded, transcribed and thematically analysed.

Results

Nineteen hospice patients successfully tried an immersive VR experience. VR sessions were acceptable for people within the hospice environment. The majority of participants enjoyed the experience. Many expressed joy and delight at the process. VR holds possibilities for relieving symptoms such as pain and anxiety frequently experienced by people in hospices. Furthermore, the technology offers the capacity to reconnect with a previous sense of self and to allow respite through the capacity to transcend current reality and connect with another meaningful reality. This exploratory study offers a starting point for larger studies to investigate the utility of VR for hospice patients.
STING agonist loaded lipid nanoparticles overcome anti-PD-1 resistance in melanoma lung metastasis via NK cell activation
Authors: Nakamura Takashi , Sato Takanori , Endo Rikito , Sasaki Shun , Takahashi Naomichi , Sato Yusuke , Hyodo Mamoru , Hayakawa Yoshihiro , Harashima Hideyoshi
Published: July 2021

Background

Resistance to an immune checkpoint inhibitor (ICI) is a major obstacle in cancer immunotherapy. The causes of ICI resistance include major histocompatibility complex (MHC)/histocompatibility locus antigen (HLA) class I loss, neoantigen loss, and incomplete antigen presentation. Elimination by natural killer (NK) cells would be expected to be an effective strategy for the treatment of these ICI-resistant tumors. We previously demonstrated that a lipid nanoparticle containing a stimulator of an interferon gene (STING) agonist (STING-LNP) efficiently induced antitumor activity via the activation of NK cells. Thus, we evaluated the potential of reducing ICI resistance by STING-LNPs.

Methods

Lung metastasis of a B16-F10 mouse melanoma was used as an anti-programmed cell death 1 (anti-PD-1)-resistant mouse model. The mice were intravenously injected with the STING-LNP and the mechanism responsible for the improvement of anti-PD-1 resistance by the STING-LNPs was analyzed by RT-qPCR and flow cytometry. The dynamics of STING-LNP were also investigated.

Results

Although anti-PD-1 monotherapy failed to induce an antitumor effect, the combination of the STING-LNP and anti-PD-1 exerted a synergistic antitumor effect. Our results indicate that the STING-LNP treatment significantly increased the expression of CD3, CD4, NK1.1, PD-1 and interferon (IFN)-γ in lung metastases. This change appears to be initiated by the type I IFN produced by liver macrophages that contain the internalized STING-LNPs, leading to the systemic activation of NK cells that express PD-1. The activated NK cells appeared to produce IFN-γ, resulting in an increase in the expression of the PD ligand 1 (PD-L1) in cancer cells, thus leading to a synergistic antitumor effect when anti-PD-1 is administered.

Conclusions

We provide a demonstration to show that a STING-LNP treatment can overcome PD-1 resistance in a B16-F10 lung metastasis model. The mechanism responsible for this indicates that NK cells are activated by stimulating the STING pathway which, in turn, induced the expression of PD-L1 on cancer cells. Based on the findings reported herein, the STING-LNP represents a promising candidate for use in combination therapy with anti-PD-1-resistant tumors.
Development of a BCS Class II Drug Microemulsion for Oral Delivery: Design, Optimization, and Evaluation
Authors: Tlijani Marwa , Lassoued Mohamed Ali , Bahloul Badr , Sfar Souad
Published: July 2021

Our work is aimed at exploring the composition and the properties of microemulsion (ME), as a drug delivery system, to enhance the permeability across the gastrointestinal (GI) barrier of fenofibrate, a BCS class II drug. It is a prodrug that is converted rapidly after oral administration into a major active metabolite which is the fenofibric acid. It undergoes a nearly complete presystemic metabolism. Its main drawback is the low bioavailability of the metabolite. A quick selection of excipients was made based on the capacity of solubilization and the value of hydrophilic-lipophilic balance. The classical method of ME development was coupled with the factorial design in order to minimize the droplet size using a low concentration of surfactant. The optimized ME showed a droplet size of 48.5 nm and physical stability. The passive permeability evaluated using Sartorius was 1.6 times higher than that of the free drug. The ex vivo technique, performed using the everted gut sac model, showed a 2.5-fold higher permeability. This suggests that the carrier-mediated uptake/efflux may present the dominant transport mechanism of fenofibrate. The use of the excipients that inhibit GI P-glycoprotein may be a new perspective. Thus, this paper shows that the composition and the characteristics of ME may be explored to increase the permeability of fenofibrate across the GI membrane.
Two-Stage Humanitarian Logistics Deprivation Model for the Planning of Scarce KN-95 Facemask Supplies under Agent’s Cooperation
Authors: Pineda-Martinez Oscar L. , Paternina-Arboleda Carlos D. , García-Llinás Guisselle A.
Published: July 2021

Humanitarian logistics encompasses a wide spectrum of conditions or constraints for supply chains, yet its focus on mitigating human suffering efficiently is what has motivated organizations and governments to make rapid decisions in real time. In this article, through the approach to an emergency such as COVID-19, we propose a two-stage model capable of considering human suffering, the cost of humanitarian logistics, and the benefit obtained by the interaction of suppliers that generally behave as oligopolies through a mathematical programming model and one of the cooperative games. Our main finding was the adaptability of a previously validated model for humanitarian logistics to the ongoing COVID-19 pandemic, where the externalities had greater relevance in social costs than private costs.
Complex Risk Statistics with Scenario Analysis
Authors: Sun Fei , Dong Yichuan
Published: July 2021

Complex risk is a critical factor for both intelligent systems and risk management. In this paper, we consider a special class of risk statistics, named complex risk statistics. Our result provides a new approach for addressing complex risk, especially in deep neural networks. By further developing the properties related to complex risk statistics, we are able to derive dual representations for such risk.
Public Perception Analysis of Hot Topics in Intellectual Property Based on Microblog Data
Authors: Dandan Shi
Published: July 2021

Public opinion is a crucial factor for government policy making, implementation, evaluation, and social development. This paper analyzes the public opinion perception of intellectual property subject based on microblog data and puts forward the concept and calculation model for the breadth, depth, and comprehensive value of public perception. Then, taking the opinion evaluation in microblog platform as an example, this paper studies the public perception of intellectual property subject and illustrates the changing trend of public perception through related events in microblog. The results show that the four topics of trademark, intellectual property, copyright, and patent are the hot topics of public perception, the breadth, depth, and comprehensive value of public perception for the four topics fluctuated greatly, on the whole. In addition, when the content of microblog is related to personal benefits, business benefits, and personal interests, it can cause widespread public concern. Additionally, the public mainly participate in the dissemination of public opinion on intellectual property subject through forwarding. Finally, this paper puts forward some suggestions from the perspective of how to maximize the effect of intellectual property policy.
Systematic Analysis of the Oncogenic Role of WDR62 in Human Tumors
Authors: Bu Yulan , Zhang Lihua , Ma Xiaolin , Wang Rui , Zhang Xuecheng , Li Jiaqiu
Published: July 2021

Background. Emerging studies support the oncogenic role of WD repeat domain 62 (WDR62) in few tumors, while no pan-cancer analysis is available. In this study, we analyzed systematically the oncogenic role of WDR62 across a series of human tumors based on bioinformatic data mining. Methods. The expression level of WDR62 was analyzed via GEPIA2, TIMER, UALCAN, and StarBase databases. The prognostic role was analyzed via GEPIA2, TIMER, UALCAN, StarBase, TISIDB, TCGA portal, Kaplan-Meier Plotter, and PrognoScan databases. Then, we explored the causes for WDR62 abnormal expression via TCGA portal and UALCAN databases. Subsequently, the STRING and GeneMANIA databases were used to find the interactive networks for WDR62. Furthermore, we analyzed the correlation between WDR62 expression and immune features via TIMER and TISIDB databases. Results. We found that WDR62 was significantly upregulated in most of the tumors and correlated with poor prognosis mainly in 6 candidate tumors—BLCA, BRCA, KIRC, KIRP, LIHC, and LUAD. Abnormal WDR62 expression may be probably attributed to TP53 mutation and promoter DNA methylation. Relative network analysis demonstrated that WDR62 was mainly involved in MAPK and toll-like receptor signaling pathway. WDR62 expression was associated with various immune cell infiltrations, especially cancer-associated fibroblasts (CAF) and T cell regulatory (Treg) cells, and was markedly correlated with poor prognosis. Moreover, WDR62 expression was closely associated with the expression of some immunomodulators such as PD-L1 and has a significant prognostic value. Conclusions. Our study revealed that WDR62 could serve as a diagnostic and prognostic biomarker for several cancers. Importantly, WDR62 was closely associated with various immune cell infiltration, and to a certain extent, it can predict the effect of immunotherapy in particular PD1/PD-L1 inhibitors. Our pan-cancer study provided useful information on the oncogenic role of WDR62, contributing to further exploring the underlying mechanisms.
Relation between Cajal Cell Density and Radiological and Scintigraphic Outcomes in Patients with Ureteropelvic Junction Obstruction
Authors: Tokat Eda , Gurocak Serhat , Akdemir Ozgur , Gonul Ipek Isik , Tan Mustafa Ozgur
Published: July 2021

Introduction: In this study, we aimed to investigate the correlation between Cajal cell density and preoperative and postoperative radiological and scintigraphic parameters in ureteropelvic junction obstruction (UPJO). Methods: The study group consisted of 41 renal units (38 consecutive patients; 13 female and 25 male) surgically treated for UPJO. UPJ specimens from patients were immuno-stained with CD117 (c-kit) antibody for interstitial Cajal cells (ICCs). The relation between Cajal cell density and preoperative and postoperative radiological and scintigraphic parameters was evaluated. Results: The mean age of the patients was 8.52 ± 8.86 (0–35) years. The density of Cajal cells was defined in 2 groups for convenient analysis as 0–5 cells (low) in 19 (46.3%) patients and >5 cells (moderate-high) in 22 (53.6%). There was significant difference between the preoperative and postoperative anteroposterior diameters of the related kidneys in both Cajal groups (p = 0.001-low, p = 0.000-moderate-high) independent of Cajal cell density. Regression in hydronephrosis postoperatively was determined in both Cajal groups (77.8%-low, 64.7%-moderate-high); however, there was no difference between them (p = 0.39). Preoperative T1/2 was significantly longer in the low Cajal group (p = 0.02). Postoperative T1/2 decreased in both low (p = 0.000) and moderate-high (p = 0.001) Cajal groups, but no difference was found between them (p = 0.24). There was significant improvement in the kidney differential function after surgery in the low Cajal density group (p = 0.015) while there was no correlation between the scintigraphic success or improvement and Cajal cell density (p = 0.51). Discussion/Conclusion: ICC deficiency/density could not be shown as a predictive factor for the determination of success rate of pyeloplasty. Despite the lack of any evidence for the degree of deficiency as an indicator for the severity of obstruction and prediction of surgical success, further studies are needed for confirmation.