bluuebunny/crossref_metadata_2025 huggingface dataset:
Cannabinoids and chronic pelvic pain in women: Focus on endometriosis
Authors: Marcu Ioana , Gee Amy , Lynn Becky
Published: July 2021

Chronic pelvic pain in women is common and frequently difficult to treat. Chronic pelvic pain often develops in the setting of endometriosis, interstitial cystitis/bladder pain syndrome, and vulvodynia. Cannabinoids are a promising treatment modality for non-cancer chronic pain, but have not been studied in women with chronic pelvic pain nor in specific chronic pelvic pain conditions. This review focuses on the interaction of the endocannabinoid system with the menstrual cycles, with endometriotic lesions, and within the bladder. Furthermore, it provides a brief overview of existing literature of the effects of endocannabinoids on chronic pain generally, with a focus on neuropathic pain. Finally, it discusses limited data available regarding the use of cannabinoids in women with chronic pelvic pain conditions. In the opinion of the authors, cannabinoids are a reasonable treatment modality for refractory chronic pelvic pain, especially if a neuropathic component is suspected. Practitioners should expect a modest effect on pain levels with an acceptable safety profile.
Multiculturalism and Antiracism in Sports? U.S. Public Opinions about Native American Team Names and Mascots and the Use of Hijabs in Sports
Authors: Knoester Chris , Rockhill Carter
Published: July 2021

Sports interactions offer contested cultural terrain where cultural citizenship is continually (re)established. Relatedly, this study uses National Sports and Society Survey data ( n = 3,993) to assess public opinions about the use of Native American team names and mascots and the allowance of Muslim women to wear hijabs in sports. Descriptive results indicate that there is considerable but mixed support for eliminating Native American team names and mascots. There is more uniform agreement for allowing hijabs in sports, although more than 20 percent of U.S. adults disagreed with allowing them. Multiple regression results show that dominant statuses and in-group identities, as well as indicators of traditionalism, are consistently associated with reduced support for the proposed changes in sports that are designed to result in multiculturalism and antiracism. Also, recognition of racial/ethnic discrimination is positively associated with support for eliminating Native American team names and mascots as well as allowing hijabs in sports.
The Policy of Free Electricity to Agriculture Sector: Implications and Perspectives of the Stakeholders in India
Authors: Fosli Jin Kathrine , Reddy A. Amarender , Rani Radhika
Published: July 2021

The Indian central government is pursuing state governments to replace free power supply to agriculture with the Direct Benefit Transfer (DBT). This article examined the free power policy from the perspective of various stakeholders and suggested alternate policies based on a field survey in the state of united Andhra Pradesh (AP), India, in the year 2018. The team interviewed all stakeholders: farmers, economists, policy experts, power distribution companies and administrators. The study team also visited four villages in AP and conducted focus group discussions with farmers to record their perceptions and alternative policy choices. The opinions are substantiated and cross-checked with the published sources. Free electricity for agriculture is seen as a lifeline in drought-prone areas as it helped them to expand the area under irrigation and increase incomes. However, many experienced huge capital expenditures in drilling-failed borewells. Other stakeholders opine that free power leads to overexploitation of groundwater, lowering groundwater levels, rising cost of drilling deep and piling up of power subsidies, and expanding water-guzzling crops like paddy even in water scarce areas, failure of borewells leading to farmer’s distress. The study suggests that replacing free power with DBT to farmers will help them maintain their incomes without overexploiting water resources.
Lockdown and Accessibility to Food in India: How Tribal Communities Lead Through the Hunger Pandemic in Koraput, Odisha
Authors: Pattanaik Nupur
Published: July 2021

The pandemic induced lockdown has affected the tribal livelihoods, nutritional disparities, malnutrition were some of the inevitable aspects observed during the pandemic. The commentary tries to depict the plights and predicaments of tribal communities during the lockdown, how they suffer from nutritional deficiencies and surmounted to hunger and poverty. The paper highlights the lockdown in Koraput Odisha India which has led to deterioration of the lives of the tribals and somehow pushed them to starvation. There have been both primary data collection through opinions of people who were available during these times and some secondary data collection through newspaper and web-articles was done. The tribal communities' livelihood was affected during the lockdown, they have been encountering food problem and there was high scarcity of nutrition as lockdown led to shut down of shops but ultimately they had tries certain empowerment paradigms like plantation at home to substitute the nutritional discrepancies. The article explores the livelihoods of these indigenous communities and the need for empowerment, devising proactive policies for high implementation programmes and prevents them from nutritional deficiencies and brings about better social wellbeing and health conditions. As food is an important element in everyone's lives the indigenous communities' right to food and the growing concerns to bridge the gap should be an important aspect for future research.
Role of Interleukin33 in Rejuvenation of Aged Neurons and Age-Related Dementias
Authors: Lou Yahuan
Published: July 2021

Late-onset Alzheimer’s disease (LOAD) is the most common age-related dementia, and its etiology remains unclear. Recent studies have linked abnormal neuronal aging to LOAD. Neurons are non-proliferative, and thus, majority of aged neurons must be rejuvenated through repairing or eliminating damaged molecules to regain their healthy status and functionalities. We discovered a surge of oxidative stress in neurons at middle age in mice. A rapid upregulation of neuronal rejuvenation is vital, while astrocyte-expressed interleukin33 (IL33), an IL1-like cytokine, is critical for this process. Thus, IL33-deficiency cripples the neuronal rejuvenation mechanisms, such as repairing DNA double strand breaks, eliminating damaged molecules by autophagy or by glymphatic drainage. IL33-deficient mice develop tau deposition and age-related dementia following a path similar to LOAD. We hypothesize that any interferences on IL33-initiated rejuvenation process for aged neurons after middle life is a potential risk for LOAD development.
Cortical metabolic and structural differences in patients with chronic migraine. An exploratory 18FDG-PET and MRI study
Authors: Torres-Ferrus Marta , Pareto Deborah , Gallardo Victor J , Cuberas-Borrós Gemma , Alpuente Alicia , Caronna Edoardo , Vila-Balló Adrià , Lorenzo-Bosquet Carles , Castell-Conesa Joan , Rovira Alex , Pozo-Rosich Patricia
Published: July 2021

Background

To describe interictal brain structural and metabolic differences between patients with episodic migraine (EM), chronic migraine (CM) and healthy controls (HC).

Methods

This is an exploratory study including right-handed age-matched women with EM, CM and HC. On the same day, a sequential interictal scan was performed with 18FDG-PET and MRI. 3D T1-weighted images were segmented with FreeSurfer, normalized to a reference atlas and the mean values of metabolism, cortical thickness (CTh) and local gyrification index (IGI) were determined. Groups were compared using age-adjusted linear models, corrected for multiple comparisons. 18FDG-PET measurements between groups were also analysed adjusting by patient’s age, CTh and lGI. The variables independently associated with diagnosis were obtained using a logistic regression analysis.

Results

Fifteen patients (8 EM, 7 CM) and 11 HC were included. Morphometric data showed an increased CTh in 6 frontal areas (L/R-Caudal Middle Frontal, L/R-Rostral Middle Frontal, L-Medial Orbitofrontal and L-Superior Frontal) in CM patients compared to HC without differences for IGI. The structural adjusted analysis in CM showed a statistically significantly hypometabolism in 9 frontal areas (L-Lateral Orbitofrontal, L/R-Medial Orbitofrontal, L-Frontal Superior, R-Frontal pole, R-Parts Triangularis, L/R-Paracentral and R-Precentral) and 7 temporal areas (L/R-Insula, L/R-Inferior temporal, L/R-Temporal pole and R-Banks superior temporal sulcus) compared to HC. EM patients presented intermediate metabolic values ​​between EM and HC (non-significant).

Conclusions

CM patients showed frontotemporal hypometabolism and increased frontal cortical thickness when compared to HC that may explain some cognitive and behavioural pain-processing and sensory integration alterations in CM patients. Combined information from sequential or simultaneous PET and MRI could optimize the study of complex functional neurological disorders such as migraine.
Case report: appendicitis induced Staphylococcus aureus and Klebsiella pneumoniae bacteremia in a young healthy male
Authors: Deodatus Jan Arne , Paas Sander Ferdinand Emiel , Wagenvoort Gerrit Hendrik Johan , de Kubber Marije Matilde
Published: July 2021

Background

Appendicitis is one of the most frequently encountered conditions at the emergency department. Distinction is made between complicated and uncomplicated appendicitis. Complicated appendicitis may cause serious intra-abdominal infection, bacteremia, or sepsis. Emergency health providers should be highly alert to any early signs indicating such complications.

Case presentation

We present the case of a healthy young male with a gangrenous appendicitis, who received antibiotics and underwent appendectomy. Blood cultures showed unequivocal Staphylococcus aureus and concomitant Klebsiella pneumoniae bacteremia requiring prolonged antibiotic treatment and further diagnostic evaluation.

Conclusions

Although rare, appendicitis can cause Staphylococcus aureus and Klebsiella pneumoniae bacteremia with extensive implications for workup and antibiotic management. Our case stresses the importance of obtaining cultures in patients with suspicion of bacteremia given its consequences for clinical management.
Prehospital time of suspected stroke patients treated by emergency medical service: a nationwide study in Thailand
Authors: Tansuwannarat Phantakan , Atiksawedparit Pongsakorn , Wibulpolprasert Arrug , Mankasetkit Natdanai
Published: July 2021

Background

This work was to study the prehospital time among suspected stroke patients who were transported by an emergency medical service (EMS) system using a national database.

Methods

National EMS database of suspected stroke patients who were treated by EMS system across 77 provinces of Thailand between January 1, 2015, and December 31, 2018, was retrospectively analyzed. Demographic data (i.e., regions, shifts, levels of ambulance, and distance to the scene) and prehospital time (i.e., dispatch, activation, response, scene, and transportation time) were extracted. Time parameters were also categorized according to the guidelines.

Results

Total 53,536 subjects were included in the analysis. Most of the subjects were transported during 06.00-18.00 (77.5%) and were 10 km from the ambulance parking (80.2%). Half of the subjects (50.1%) were served by advanced life support (ALS) ambulance. Median total time was 29 min (IQR 21, 39). There was a significant difference of median total time among ALS (30 min), basic (27 min), and first responder (28 min) ambulances, Holm P = 0.009. Although 91.7% and 88.3% of the subjects had dispatch time ≤ 1 min and activation time ≤ 2 min, only 48.3% had RT ≤ 8 min. However, 95% of the services were at the scene ≤ 15 min.

Conclusion

Prehospital time from EMS call to hospital was approximately 30 min which was mainly utilized for traveling from the ambulance parking to the scene and transporting patients from the scene to hospitals. Even though only 48% of the services had RT ≤ 8 min, 95% of them had the scene time ≤ 15 min.
A tubby-like protein CsTLP8 acts in the ABA signaling pathway and negatively regulates osmotic stresses tolerance during seed germination
Authors: Li Shuangtao , Wang Zhirong , Wang Fei , Lv Hongmei , Cao Meng , Zhang Na , Li Fengju , Wang Hao , Li Xingsheng , Yuan Xiaowei , Zhao Bing , Guo Yang-Dong
Published: July 2021

Background

TLPs (Tubby-like proteins) are widespread in eukaryotes and highly conserved in plants and animals. TLP is involved in many biological processes, such as growth, development, biotic and abiotic stress responses, while the underlying molecular mechanism remains largely unknown. In this paper we characterized the biological function of cucumber (Cucumis sativus L.) Tubby-like protein 8 (CsTLP8) in Arabidopsis.

Results

In cucumber, the expression of the tubby-like protein CsTLP8 was induced by NaCl treatment, but reduced by PEG (Polyethylene Glycol) and ABA (Abscisic Acid) treatment. Subcellular localization and transcriptional activation activity analysis revealed that CsTLP8 possessed two characteristics of classical transcription factors: nuclear localization and trans-activation activity. Yeast two-hybrid assay revealed interactions of CsTLP8 with CsSKP1a and CsSKP1c, suggesting that CsTLP8 might function as a subunit of E3 ubiquitin ligase. The growth activity of yeast with ectopically expressed CsTLP8 was lower than the control under NaCl and mannitol treatments. Under osmotic and salt stresses, overexpression of CsTLP8 inhibited seed germination and the growth of Arabidopsis seedlings, increased the content of MDA (Malondialdehyde), and decreased the activities of SOD (Superoxide Dismutase), POD (Peroxidase) and CAT (Catalase) in Arabidopsis seedlings. Overexpression of CsTLP8 also increased the sensitivity to ABA during seed germination and ABA-mediated stomatal closure.

Conclusion

Under osmotic stress, CsTLP8 might inhibit seed germination and seedling growth by affecting antioxidant enzymes activities. CsTLP8 acts as a negative regulator in osmotic stress and its effects may be related to ABA.
Subclinical cardiac perforation by cardiac implantable electronic device leads detected by cardiac computed tomography
Authors: Lim Yeong-Min , Uhm Jae-Sun , Kim Min , Kim In-Soo , Jin Moo-Nyun , Yu Hee Tae , Kim Tae-Hoon , Lee Hye-Jeong , Kim Young-Jin , Joung Boyoung , Pak Hui-Nam , Lee Moon-Hyoung
Published: July 2021

Background

The relationship between the characteristics of cardiac implantable electronic device (CIED) leads and subclinical cardiac perforations remains unclear. This study aimed to evaluate the incidence of subclinical cardiac perforation among various CIED leads using cardiac computed tomography (CT).

Methods

A total of 271 consecutive patients with 463 CIED leads, who underwent cardiac CT after CIED implantation, were included in this retrospective observational study. Cardiac CT images were reviewed by one radiologist and two cardiologists. Subclinical perforation was defined as traversal of the lead tip past the outer myocardial layer without symptoms and signs related to cardiac perforation. We compared the subclinical cardiac perforation rates of the available lead types.

Results

A total of 219, 49, and 3 patients had pacemakers, implantable cardioverter-defibrillators, and cardiac resynchronization therapy, respectively. The total subclinical cardiac perforation rate was 5.6%. Subclinical cardiac perforation by screw-in ventricular leads was significantly more frequent than that caused by tined ventricular leads (13.3% vs 3.3%, respectively, p = 0.002). There were no significant differences in the incidence of cardiac perforation between atrial and ventricular leads, screw-in and tined atrial leads, pacing and defibrillator ventricular leads, nor between magnetic resonance (MR)-conditional and MR-unsafe screw-in ventricular leads. Screw-in ventricular leads were significantly associated with subclinical cardiac perforation [odds ratio, 4.554; 95% confidence interval, 1.587–13.065, p = 0.005]. There was no case subclinical cardiac perforation by septal ventricular leads.

Conclusions

Subclinical cardiac perforation by screw-in ventricular leads is not rare. Septal pacing may be helpful in avoiding cardiac perforation.
Weather conditions associated with subarachnoid hemorrhage: a multicenter case-crossover study
Authors: Kockler Michael , Schlattmann Peter , Walther Mario , Hagemann Georg , Becker Philipp Nils , Rosahl Steffen , Witte Otto W. , Schwab Matthias , Rakers Florian
Published: July 2021

Background

Most spontaneous subarachnoid hemorrhages (SAH) occur unexpectedly and independently of classical risk factors. In the light of increasing climate variability and change, we investigated weather and rapid weather changes as possible short-term risk factors for SAH.

Methods

Seven hundred ninety one patients admitted to three major hospitals in Germany for non-traumatic SAH with a determinable onset of SAH symptoms were included in this hospital-based, case-crossover study. The effects of atmospheric pressure, relative air humidity, and ambient temperature and their 24 h changes on the onset of SAH under temperate climate conditions were estimated.

Results

There was no association between the risk of SAH and 24 h weather changes, mean daily temperature or mean relative air humidity in the overall population. For every 11.5 hPa higher mean daily atmospheric pressure, the risk of SAH increased by 15% (OR 1.15, 95% confidence interval (CI) 1.01–1.30) in the entire study population with a lag time of three days.

Conclusion

Our results suggest no relevant association between 24 h-weather changes or absolute values of ambient temperature and relative humidity and the risk of SAH. The medical significance of the statistically weak increase in SAH risk three days after exposure to high atmospheric pressure is unclear. However, as the occurrence of stable high-pressure systems will increase with global warming and potentially affect SAH risk, we call for confirming studies in different geographical regions to verify our observations.
A qualitative evaluation of Southwark Council’s public health response to mitigating the mental health impact of the 2017 London bridge and borough market terror attack
Authors: Jumbe Sandra , Milner Adrienne , Clinch Megan , Kennedy Jonathan , Pinder Richard J. , Sharpe Carolyn A. , Fenton Kevin
Published: July 2021

Background

Over recent years there have been several major terror attacks in cities across Europe. These attacks result in deaths, physical injuries, and pose long-term threats to mental health and wellbeing of large populations. Although psychologists have completed important work on mental health responses to disaster exposure including terrorist attacks, the mental health impacts of such attacks have been comparatively less examined in academic literature than the acute health response to physical injuries. This paper reflects on Southwark Council’s pioneering public mental health response to the June 2017 terror attack at London Bridge and Borough Market. It aims to explore perceptions of the mental health impact of the incident by those living and working in the borough.

Methods

A rapid qualitative evaluation informed by the logic underpinning Southwark Council’s response was conducted. Seven formative interviews were undertaken with individuals involved in the response planning and/or delivery, enabling the evaluation team to establish the response’s theoretical basis. Subsequently, nineteen semi-structured interviews with consenting Council employees, residents, business owners, and workers from the Borough were conducted to understand perceived mental health impacts of the attack and the success of the Council response. Thematic analysis of transcribed interviews was undertaken to evaluate the extent to which the response was implemented successfully.

Results

Participants reported feeling the attack had a wide-reaching negative impact on the mental health of residents, those working in the borough and visitors who witnessed the attack. Delivering the response was a challenge and response visibility within the community was limited. Participants suggested a comprehensive systematic approach to health needs assessment informed by knowledge and relationships of key Council workers and community stakeholders is imperative when responding to terrorist incidents. Improved communication and working relationships between statutory organisations and community stakeholders would ensure community groups are better supported. Prioritising mental health needs of terror attack responders to mitigate persisting negative impacts was highlighted.

Conclusions

This article highlights a potential public health approach and need for developing robust practical guidance in the aftermath of terror attacks. This approach has already influenced the response to the Christchurch mosque shooting in 2019.
Preliminary results in anterior cervical discectomy and fusion with the uncovertebral joint fusion cage in a goat model
Authors: Shen Yi-Wei , Yang Yi , Liu Hao , Wu Ting-Kui , Ma Li-Tai , Chen Lin , Hu Ling-Yun , Ding Chen , Rong Xin , Wang Bei-Yu , Meng Yang , Hong Ying
Published: July 2021

Objective

To preliminarily evaluate the safety and efficacy of the uncovertebral joint fusion cage in a goat model of cervical spine interbody fusion.

Methods

Twenty-four healthy adult goats were randomly assigned to one of the two following groups: Group A, goats were implanted with an uncovertebral joint fusion cage combined with a local autograft and Group B, goats were implanted with a non-profile cage filled with a local autograft. The goats were prospectively evaluated for 24 weeks and then were sacrificed for evaluation. X-rays, CT and micro-CT scanning, and undecalcified bone histological analysis were used for the evaluation of fusion.

Results

75.0% (9/12) of the goats in Group A were evaluated as having fusion at 12 weeks, compared to 41.7% (5/12) in Group B. 83.3% (10/12) of the goats in Group A were evaluated as having fusion at 24 weeks compared to 58.3% (7/12) in Group B. The fusion grading scores in Group A were significantly higher than that in Group B both at 12 weeks and 24 weeks (P < 0.05). Micro-CT scanning and undecalcified bone histological analysis showed that new bone formation can be obviously found in the bilateral uncovertebral joint. The bone volume fraction (BV/ TV) in Group A (23.59 ± 4.43%) was significantly higher than Group B (16.16 ± 4.21%), with P < 0.05.

Conclusions

Preliminary results of this study demonstrated that uncovertebral joint fusion cage is effective for achieving early bone formation and fusion without increase of serious complications.
Prognostic validity of the Periapical and Endodontic Status Scale for the radiographically assessed 2-year treatment outcomes in teeth with apical periodontitis: a prospective clinical study
Authors: Gudac Jelena , Hellén-Halme Kristina , Machiulskiene Vita
Published: July 2021

Background

Endodontic treatment planning and treatment success evaluation are largely based on radiographic assessment of anatomical and treatment-related parameters of teeth with apical periodontitis (AP). This prospective clinical study aimed to assess radiographically the 2-year endodontic treatment outcomes for teeth with AP, and to evaluate prognostic validity of Periapical and Endodontic Status Scale (PESS).

Methods

A total of 128 patients, representing 176 teeth with AP were examined by cone-beam computed tomography at baseline and at 24 months after endodontic treatment. Treatment outcome was evaluated using estimates of periapical radiolucency and the relationship between anatomical structures and location. The strength of the associations between these and treatment-related parameters was tested by logistic regression analysis. PESS sensitivity and specificity were calculated for every treatment risk group (low, moderate, high) of teeth.

Results

One hundred and fifty-seven teeth, representing 350 root canals had a positive treatment outcome, while 19 teeth, representing 53 root canals had a negative treatment outcome at 24 months. The probability of negative outcome was 25 times higher in the moderate/high-risk group than in the mild-risk group of teeth (OR = 25.1; 95%CI [12.2–51.5]). Pre-treatment complications and retreatment cases with radiolucency were associated with negative outcomes (OR = 35.9; 95%CI [12.6–102.4]; OR = 26.437; 95%CI [10.9–64.1], respectively). PESS sensitivity and specificity was over 80% in all risk groups except for high risk group, due to very low number of cases.

Conclusions

Endodontic treatment outcome depends on the severity of periapical changes. The presence of complications and retreatment cases with periapical lesions are associated with negative treatment outcome. The PESS is a valid instrument to predict outcome of teeth with low-moderate treatment risk of AP.
Challenges and proposed solutions in making clinical research on COVID-19 ethical: a status quo analysis across German research ethics committees
Authors: Faust Alice , Sierawska Anna , Krüger Katharina , Wisgalla Anne , Hasford Joerg , Strech Daniel
Published: July 2021

Background

In the course of the COVID-19 pandemic, the biomedical research community’s attempt to focus the attention on fighting COVID-19, led to several challenges within the field of research ethics. However, we know little about the practical relevance of these challenges for Research Ethics Committees (RECs).

Methods

We conducted a qualitative survey across all 52 German RECs on the challenges and potential solutions with reviewing proposals for COVID-19 studies. We de-identified the answers and applied thematic text analysis for the extraction and synthesis of challenges and potential solutions that we grouped under established principles for clinical research ethics.

Results

We received an overall response rate of 42%. The 22 responding RECs reported that they had assessed a total of 441 study proposals on COVID-19 until 21 April 2020. For the review of these proposals the RECs indicated a broad spectrum of challenges regarding (1) social value (e.g. lack of coordination), (2) scientific validity (e.g. provisional study planning), (3) favourable risk–benefit ratio (e.g. difficult benefit assessment), (4) informed consent (e.g. strict isolation measures), (5) independent review (e.g. lack of time), (6) fair selection of trial participants (e.g. inclusion of vulnerable groups), and (7) respect for study participants (e.g. data security). Mentioned solutions ranged from improved local/national coordination, over guidance on modified consent procedures, to priority setting across clinical studies.

Conclusions

RECs are facing a broad spectrum of pressing challenges in reviewing COVID-19 studies. Some challenges for consent procedures are well known from research in intensive care settings but are further aggravated by infection measures. Other challenges such as reviewing several clinical studies at the same time that potentially compete for the recruitment of in-house COVID-19 patients are unique to the current situation. For some of the challenges the proposed solutions in our survey could relatively easy be translated into practice. Others need further conceptual and empirical research. Our findings together with the increasing body of literature on COVID-19 research ethics, and further stakeholder engagement should inform the development of hands-on guidance for researchers, funders, RECs, and further oversight bodies.
Alternative oxidase gene induced by nitric oxide is involved in the regulation of ROS and enhances the resistance of Pleurotus ostreatus to heat stress
Authors: Hou Ludan , Zhao Mengran , Huang Chenyang , He Qi , Zhang Lijiao , Zhang Jinxia
Published: July 2021

Background

In China, during the cultivation process of Pleurotus ostreatus, the yield and quality of fruiting bodies are easily affected by high temperatures in summer. Nitric oxide (NO) plays an important regulatory role in the response to abiotic stress, and previous studies have found that NO can induce alternative oxidase (aox) experssion in response to heat stress (HS) by regulating aconitase. However, the regulatory pathway of NO is complex, and the function and regulation of the aox gene in the response to HS remain unclear.

Results

In this study, we found that NO affected nicotinamide adenine dinucleotide (NADH) and adenosine triphosphate (ATP) levels, reduced hydrogen peroxide (H2O2) and superoxide anion (O2−) contents, and slowed O2− production. Further RNA-Seq results showed that NO regulated the oxidation-reduction process and oxidoreductase activity, affected the cellular respiration pathway and activated aox gene expression. The function of aox was determined by constructing overexpression (OE) and RNA interference (RNAi) strains. The results showed that the OE-aox strains exhibited obviously improved growth recovery after exposure to HS. During exposure to HS, the OE-aox strains exhibited reduced levels of NADH, the product of the tricarboxylic acid (TCA) cycle, and decreased synthesis of ATP, which reduced the production and accumulation of reactive oxygen species (ROS), whereas the RNAi-aox strains exhibited the opposite result. In addition, aox mediated the expression of antioxidant enzyme genes in the mycelia of P. ostreatus under HS through the retrograde signaling pathway.

Conclusions

This study shows that the expression of the aox gene in P. ostreatus mycelia can be induced by NO under HS, that it regulates the TCA cycle and cell respiration to reduce the production of ROS, and that it can mediate the retrograde signaling pathway involved in the mycelial response to HS.

Graphical abstract
CircFBXL5 promotes the 5-FU resistance of breast cancer via modulating miR-216b/HMGA2 axis
Authors: Zhu Mingzhi , Wang Yanyan , Wang Fang , Li Lin , Qiu Xinguang
Published: July 2021

Background

Circular RNAs (circRNAs) have been confirmed to be relevant to the 5-fluorouracil (5-FU) resistance of breast cancer. Nevertheless, how and whether circRNA F-box and leucine-rich repeat protein 5 (circFBXL5) regulates the 5-FU resistance of breast cancer is uncertain. This study aims to explore the function and mechanism of circFBXL5 in the 5-FU resistance of breast cancer.

Methods

Thirty nine paired breast cancer and normal tissues were harvested. circFBXL5, microRNA-216b (miR-216b) and high-mobility group AT-hook 2 (HMGA2) abundances were examined via quantitative reverse transcription polymerase chain reaction or western blot. Cell viability, 5-FU resistance, migration, invasion, and apoptosis were tested via cell counting kit-8 assay, wound healing analysis, transwell analysis, and flow cytometry. The relationship of miR-216b and circFBXL5 or HMGA2 was tested via dual-luciferase reporter analysis and RNA pull-down assay. The impact of circFBXL5 on breast cancer tumor growth in vivo was analyzed via xenograft model.

Results

circFBXL5 was highly expressed in breast cancer tissues and cells, and was more upregulated in 5-FU-resistant breast cancer cells. Function experiments showed that circFBXL5 knockdown inhibited the 5-FU resistance of breast cancer by inhibiting cell migration, invasion and promoting apoptosis. In the terms of mechanism, miR-216b could be sponged by circFBXL5, and its inhibitor could also reverse the influence of circFBXL5 silencing on the 5-FU resistance of breast cancer cells. In addition, HMGA2 was a target of miR-216b, and its overexpression also reversed the regulation of miR-216b overexpression on the 5-FU resistance of breast cancer. Furthermore, circFBXL5 interference declined breast cancer tumor growth in xenograft model.

Conclusion

Our data showed that circFBXL5 could promote the 5-FU resistance of breast cancer by regulating miR-216b/HMGA2 axis.
Is there evidence of anti-malarial multidrug resistance in Burkina Faso?
Authors: Rasmussen Charlotte , Ringwald Pascal
Published: July 2021

Recently, Gansané and colleagues published an article on inadequate efficacy of two different forms of artemisinin-based combination therapy (ACT) in Burkina Faso. The development ofPlasmodium falciparumresistance to different ACT partner drugs at levels that could affect the efficacy of two ACT would both be startling and a cause for great concern. In reviewing the available data collected since 2008 on ACT efficacy in Burkina Faso, the analysis shows that the reported efficacy of the tested ACT varies greatly. Most of the studies have considerable methodological deviations and challenges, especially in PCR correction done to distinguish between recrudescence and re-infection, and in the failure to omit re-infections in the calculation of efficacy rates. So far, there is no convincing evidence in the articles reviewed that multidrug resistance has emerged in Burkina Faso. However, the potential consequence of failing ACT means that the results published by Gansané et al. urgently need to be confirmed. Furthermore, articles reporting on efficacy data need to include an examination of the potential consequences of any methodological deviations.
Comparing the monetary value of a quality-adjusted life year from the payment card and the open-ended format
Authors: Ye Ziping , Liu Fuyao , Ma Jia , Zhou Ziyang , Wang Chen , Sun Lihua
Published: July 2021

Background

The payment card (PC) format and the open-ended (OE) format are common methods in eliciting willingness-to-pay (WTP) of one additional quality-adjusted life year (QALY). The aim of this research is to compare these two formats in eliciting the monetary value of a QALY.

Methods

A contingent valuation survey was carried out using a pre-designed questionnaire with various hypothetical scenarios. The difference between the PC and the OE formats was evaluated by a two-sample equality test. Furthermore, generalized linear models were carried out to control observed heterogeneity and to test theoretical validity.

Results

In total, 461 individuals were involved, among whom 235 (51%) answered the PC question, while 226 (49%) answered the OE question. Excluding zero response, the mean WTP values of these two formats for different scenarios varied dramatically, which was from 13,278 to 280,177 RMB for the PC, 18,119 to 620,913 RMB for the OE. The OE format tended to elicit lower values for less serious condition and higher values for more serious condition. However, equality test of mean and median demonstrated insignificant difference of these two formats for all scenarios. For both OE and PC format, most variables were found to have significant effect on the value of WTP/QALY. Moreover, joint estimation indicated a statistically significant positive effect on the OE results. Further analysis demonstrated that the imbalanced zero response distribution caused the main difference of these two formats.

Conclusions

This research indicated insignificantly different WTP/QALY estimates of the PC format and OE format with the grouped data whereas significantly higher estimates of the OE format from the pooled data. These two formats were found to be valid. More research about the difference and the validity of various WTP eliciting methods would be recommended for a robust estimation of WTP/QALY.
The role of exosomes in lung cancer metastasis and clinical applications: an updated review
Authors: Yin Lei , Liu Xiaotian , Shao Xuejun , Feng Tao , Xu Jun , Wang Qi , Hua Shenghao
Published: July 2021

Lung cancer is the leading cause of cancer-associated deaths accounting for 24% of all cancer deaths. As a crucial phase of tumor progression, lung cancer metastasis is linked to over 70% of these mortalities. In recent years, exosomes have received increasing research attention in their role in the induction of carcinogenesis and metastasis in the lung. In this review, recent studies on the contribution of exosomes to lung cancer metastasis are discussed, particularly highlighting the role of lung tumor-derived exosomes in immune system evasion, epithelial-mesenchymal transition, and angiogenesis, and their involvement at both the pre-metastatic and metastatic phases. The clinical application of exosomes as therapeutic drug carriers, their role in antitumor drug resistance, and their utility as predictive biomarkers in diagnosis and prognosis are also presented. The metastatic activity, a complex multistep process of cancer cell invasion, survival in blood vessels, attachment and subsequent colonization of the host's organs, is integrated with exosomal effects. Exosomes act as functional mediating factors in cell–cell communication, influencing various steps of the metastatic cascade. To this end, lung cancer cell-derived exosomes enhance cell proliferation, angiogenesis, and metastasis, regulate drug resistance, and antitumor immune activities during lung carcinogenesis, and are currently being explored as an important component in liquid biopsy assessment for diagnosing lung cancer. These nano-sized extracellular vesicles are also being explored as delivery vehicles for therapeutic molecules owing to their unique properties of biocompatibility, circulatory stability, decreased toxicity, and tumor specificity. The current knowledge of the role of exosomes highlights an array of exosome-dependent pathways and cargoes that are ripe for exploiting therapeutic targets to treat lung cancer metastasis, and for predictive value assessment in diagnosis, prognosis, and anti-tumor drug resistance.
Characterization of genomic alterations in Chinese colorectal cancer patients with liver metastases
Authors: Wang Hong-Wei , Yan Xiao-Luan , Wang Li-Jun , Zhang Meng-Huan , Yang Chun-He , Wei-Liu  , Jin Ke-Min , Bao Quan , Li Juan , Wang Kun , Xing Bao-Cai
Published: July 2021

Background

The exploration of genomic alterations in Chinese colorectal liver metastasis (CRLM) is limited, and corresponding genetic biomarkers for patient’s perioperative management are still lacking. This study aims to understand genome diversification and complexity that developed in CRLM.

Methods

A custom-designed IDT capture panel including 620 genes was performed in the Chinese CRLM cohort, which included 396 tumor samples from metastatic liver lesions together with 133 available paired primary tumors.

Results

In this Chinese CRLM cohort, the top-ranked recurrent mutated genes were TP53 (324/396, 82%), APC (302/396, 76%), KRAS (166/396, 42%), SMAD4 (54/396, 14%), FLG (52/396, 13%) and FBXW7 (43/396, 11%). A comparison of CRLM samples derived from left- and right-sided primary lesions confirmed that the difference in survival for patients with different primary tumor sites could be driven by variations in the transforming growth factor β (TGF-β), phosphatidylinositol 3-kinase (PI3K) and RAS signaling pathways. Certain genes had a higher variant rate in samples with metachronous CRLM than in samples with simultaneous metastasis. Overall, the metastasis and primary tumor samples displayed highly consistent genomic alterations, but there were some differences between individually paired metastases and primary tumors, which were mainly caused by copy number variations.

Conclusion

We provide a comprehensive depiction of the genomic alterations in Chinese patients with CRLM, providing a fundamental basis for further personalized therapy applications.
COVID-19 in Ghana: challenges and countermeasures for maternal health service delivery in public health facilities
Authors: Agbozo Faith , Jahn Albrecht
Published: July 2021

We provide a situational update on COVID-19 in Ghana, the seventh African country reporting the most cases. Some modifications occurring within the health system to curtail the outbreak and its potential impact on the delivery of antenatal care services are also highlighted. With the discovery of the Delta variant in Ghana, the current attention is to prevent a third wave of infection, and also control and manage existing cases. Efforts to procure vaccines, vaccinate special populations and sensitize the public on the implications of vaccine hesitancy are ongoing. Amidst these activities, we suggest some innovations and countermeasures to safeguard primary healthcare services and potentially reinvest efforts towards achieving the sustainable development goal three within the context of maternal healthcare, citing examples specific to developing countries.
Whatever can go wrong, need not go wrong: Open Quality approach for epidemiology
Authors: Alba Sandra , Straetemans Masja
Published: July 2021

Quality assurance is one of the most important aspects of an epidemiological study, as its validity is largely determined by data quality. The mounting success of quality management in the industrial sector caused a rapid spread throughout manufacturing industries and beyond. Yet, little has been published so far on quality assurance in epidemiology. In this article we review three models for quality assurance (Juran, Donabedian and ISO 9000) and showcase how these can be brought together in one intuitive, systematic and flexible approach to quality assurance in epidemiology. The resulting Open Quality approach refers back to the three processes identified by Juran (planning, control and verification). During the planning stage, we propose a subdivision of the study process in a set of steps and a definition of quality attributes corresponding to activities in that step as suggested by the ISO approach. We refer to the Donabedian model to determine the level at which the control/monitoring should take place—structure, processes or outcomes. Along with an overview of the Open Quality approach we propose an Open Quality tool to support the definition of quality attributes, failure modes, preventive strategies, verification activities, and corrective actions, which form the backbone of the Open Quality approach.
Data-driven approach for tailoring facilitation strategies to overcome implementation barriers in community pharmacy
Authors: Moussa Lydia , Benrimoj Shalom , Musial Katarzyna , Kocbek Simon , Garcia-Cardenas Victoria
Published: July 2021

Background

Implementation research has delved into barriers to implementing change and interventions for the implementation of innovation in practice. There remains a gap, however, that fails to connect implementation barriers to the most effective implementation strategies and provide a more tailored approach during implementation. This study aimed to explore barriers for the implementation of professional services in community pharmacies and to predict the effectiveness of facilitation strategies to overcome implementation barriers using machine learning techniques.

Methods

Six change facilitators facilitated a 2-year change programme aimed at implementing professional services across community pharmacies in Australia. A mixed methods approach was used where barriers were identified by change facilitators during the implementation study. Change facilitators trialled and recorded tailored facilitation strategies delivered to overcome identified barriers. Barriers were coded according to implementation factors derived from the Consolidated Framework for Implementation Research and the Theoretical Domains Framework. Tailored facilitation strategies were coded into 16 facilitation categories. To predict the effectiveness of these strategies, data mining with random forest was used to provide the highest level of accuracy. A predictive resolution percentage was established for each implementation strategy in relation to the barriers that were resolved by that particular strategy.

Results

During the 2-year programme, 1131 barriers and facilitation strategies were recorded by change facilitators. The most frequently identified barriers were a ‘lack of ability to plan for change’, ‘lack of internal supporters for the change’, ‘lack of knowledge and experience’, ‘lack of monitoring and feedback’, ‘lack of individual alignment with the change’, ‘undefined change objectives’, ‘lack of objective feedback’ and ‘lack of time’. The random forest algorithm used was able to provide 96.9% prediction accuracy. The strategy category with the highest predicted resolution rate across the most number of implementation barriers was ‘to empower stakeholders to develop objectives and solve problems’.

Conclusions

Results from this study have provided a better understanding of implementation barriers in community pharmacy and how data-driven approaches can be used to predict the effectiveness of facilitation strategies to overcome implementation barriers. Tailored facilitation strategies such as these can increase the rate of real-time implementation of innovations in healthcare, leading to an industry that can confidently and efficiently adapt to continuous change.
West meets east: open up a dialogue on phytomedicine
Authors: Li Xiuzhu , Chen Weijie , Simal-Gandara Jesus , Georgiev Milen I. , Li Hongyi , Hu Hao , Wu Xu , Efferth Thomas , Wang Shengpeng
Published: July 2021

The desire to extend the wisdom of traditional health systems has motivated the trade of many phytomedicine on a global scale for centuries, especially some dietary herbs, making a great overlap exits between western and eastern phytomedicine. Despite the communication since ancient times, a key disconnect still exists in the dialog among western and eastern herbal researchers. There is very little systematic effort to tap into the friction and fusion of eastern and western wisdom in utilizing phytomedicine. In this review, we analyzed the similarities and differences of three representative phytomedicine, namely Rhodiola, seabuckthorn, and fenugreek, aiming to open up new horizons in developing novel health products by integrating the wisdom of the east and the west.
Modeling temperature- and Cav3 subtype-dependent alterations in T-type calcium channel mediated burst firing
Authors: Fernandez Fernando R. , Iftinca Mircea C. , Zamponi Gerald W. , Turner Ray W.
Published: July 2021

T-type calcium channels are important regulators of neuronal excitability. The mammalian brain expresses three T-type channel isoforms (Cav3.1, Cav3.2 and Cav3.3) with distinct biophysical properties that are critically regulated by temperature. Here, we test the effects of how temperature affects spike output in a reduced firing neuron model expressing specific Cav3 channel isoforms. The modeling data revealed only a minimal effect on baseline spontaneous firing near rest, but a dramatic increase in rebound burst discharge frequency for Cav3.1 compared to Cav3.2 or Cav3.3 due to differences in window current or activation/recovery time constants. The reduced response by Cav3.2 could optimize its activity where it is expressed in peripheral tissues more subject to temperature variations than Cav3.1 or Cav3.3 channels expressed prominently in the brain. These tests thus reveal that aspects of neuronal firing behavior are critically dependent on both temperature and T-type calcium channel subtype.