bluuebunny/crossref_metadata_2025 huggingface dataset:
Quantifying contact patterns in response to COVID-19 public health measures in Canada
Authors: Brankston Gabrielle , Merkley Eric , Fisman David N. , Tuite Ashleigh R. , Poljak Zvonimir , Loewen Peter J. , Greer Amy L.
Published: November 2021

Background

A variety of public health measures have been implemented during the COVID-19 pandemic in Canada to reduce contact between individuals. The objective of this study was to provide empirical contact pattern data to evaluate the impact of public health measures, the degree to which social contacts rebounded to normal levels, as well as direct public health efforts toward age- and location-specific settings.

Methods

Four population-based cross-sectional surveys were administered to members of a paid panel representative of Canadian adults by age, gender, official language, and region of residence during May (Survey 1), July (Survey 2), September (Survey 3), and December (Survey 4) 2020. A total of 4981 (Survey 1), 2493 (Survey 2), 2495 (Survey 3), and 2491 (Survey 4) respondents provided information about the age and setting for each direct contact made in a 24-h period. Contact matrices were constructed and contacts for those under the age of 18 years imputed. The next generation matrix approach was used to estimate the reproduction number (Rt) for each survey. Respondents with children under 18 years estimated the number of contacts their children made in school and extracurricular settings.

Results

Estimated Rt values were 0.49 (95% CI: 0.29–0.69) for May, 0.48 (95% CI: 0.29–0.68) for July, 1.06 (95% CI: 0.63–1.52) for September, and 0.81 (0.47–1.17) for December. The highest proportion of reported contacts occurred within the home (51.3% in May), in ‘other’ locations (49.2% in July) and at work (66.3 and 65.4% in September and December). Respondents with children reported an average of 22.7 (95% CI: 21.1–24.3) (September) and 19.0 (95% CI 17.7–20.4) (December) contacts at school per day per child in attendance.

Conclusion

The skewed distribution of reported contacts toward workplace settings in September and December combined with the number of reported school-related contacts suggest that these settings represent important opportunities for transmission emphasizing the need to support and ensure infection control procedures in both workplaces and schools.
Clinical outcomes of intravenous immunoglobulin therapy in COVID-19 related acute respiratory distress syndrome: a retrospective cohort study
Authors: Ali Husain S. , Elshafei Moustafa S. , Saad Mohamed O. , Mitwally Hassan A. , Al Wraidat Mohammad , Aroos Asra , Shaikh Nissar , Ananthegowda Dore C. , Abdelaty Mohamed A. , George Saibu , Nashwan Abdulqadir J. , Mohamed Ahmed S. , Khatib Mohamad Y.
Published: November 2021

Background

Intravenous immunoglobulin (IVIG) has been used as an immunomodulatory therapy to counteract severe systemic inflammation in coronavirus disease 2019 (COVID-19). But its use in COVID-19 related acute respiratory distress syndrome (ARDS) is not well established.

Methods

We conducted a retrospective analysis of electronic health records of COVID-19 patients admitted to intensive care units (ICUs) at Hazm Mebaireek General Hospital, Qatar, between March 7, 2020 and September 9, 2020. Patients receiving invasive mechanical ventilation for moderate-to-severe ARDS were divided into two groups based on whether they received IVIG therapy or not. The primary outcome was all-cause ICU mortality. Secondary outcomes studied were ventilator-free days and ICU-free days at day-28, and incidence of acute kidney injury (AKI). Propensity score matching was used to adjust for confounders, and the primary outcome was compared using competing-risks survival analysis.

Results

Among 590 patients included in the study, 400 received routine care, and 190 received IVIG therapy in addition to routine care. One hundred eighteen pairs were created after propensity score matching with no statistically significant differences between the groups. Overall ICU mortality in the study population was 27.1%, and in the matched cohort, it was 25.8%. Mortality was higher among IVIG-treated patients (36.4% vs. 15.3%; sHR 3.5; 95% CI 1.98–6.19; P < 0.001). Ventilator-free days and ICU-free days at day-28 were lower (P < 0.001 for both), and incidence of AKI was significantly higher (85.6% vs. 67.8%; P = 0.001) in the IVIG group.

Conclusion

IVIG therapy in mechanically ventilated patients with COVID-19 related moderate-to-severe ARDS was associated with higher ICU mortality. A randomized clinical trial is needed to confirm this observation further.
Hospital admission trends due to respiratory diseases in England and Wales between 1999 and 2019: an ecologic study
Authors: Naser Abdallah Y. , Mansour Munthir M. , Alanazi Abeer F. R. , Sabha Omar , Alwafi Hassan , Jalal Zahraa , Paudyal Vibhu , Dairi Mohammad S. , Salawati Emad M. , Alqahtan Jaber S. , Alaamri Shalan , Mustafa Ali Moaath K.
Published: November 2021

Background

Identifying trends of hospital admissions for respiratory diseases is crucial for public health and research to guide future clinical improvements for better outcomes. This study aims to define the trends of respiratory disease-related hospital admissions (RRHA) in England and Wales between 1999 and 2019.

Methods

An ecological study was conducted using hospital admission data taken from the Hospital Episode Statistics database in England and the Patient Episode Database for Wales. Hospital admissions data for respiratory diseases were extracted for the period between April 1999 and March 2019. The trend in hospital admissions was assessed using a Poisson model.

Results

Hospital admission rate increased by 104.7% [from 1535.05 (95% CI 1531.71–1538.38) in 1999 to 3142.83 (95% CI 3138.39–3147.26) in 2019 per 100,000 persons, trend test, p < 0.01]. The most common causes were influenza and pneumonia, chronic lower respiratory diseases, other acute lower respiratory infections, which accounted for 26.6%, 26.4%, and 14.9%, respectively. The age group 75 years and above accounted for 34.1% of the total number of hospital admissions. Males contributed to 50.5% of the total number of hospital admissions. Hospital admission rate in females increased by 119.8% [from 1442.18 (95% CI 1437.66–1446.70) in 1999 to 3169.38 (95% CI 3163.11–3175.64) in 2019 per 100,000 persons, trend test, p < 0.001]. Hospital admission rate increased by 92.9% in males [from 1633.25 (95% CI 1628.32–1638.17) in 1999 to 3149.78 (95% CI 3143.46–3156.09) in 2019 per 100,000 persons, trend test, p < 0.001].

Conclusion

During the study period, hospital admissions rate due to respiratory diseases increased sharply. The rates of hospital admissions were higher among males for the vast majority of respiratory diseases. Further observational studies are warranted to identify risk factors for these hospital admissions and to offer relevant interventions to mitigate the risk.
Prevalence, risk factors, and management practices of primary dysmenorrhea among young females
Authors: Karout Samar , Soubra Lama , Rahme Deema , Karout Lina , Khojah Hani M J , Itani Rania
Published: November 2021

Background

Primary dysmenorrhea (PD) is one of the most common gynecological conditions among young females, which has a significant negative impact on health-related quality of life and productivity. Despite its high prevalence, the evidence is limited regarding the management-seeking practices and its perceived effectiveness among females with PD.

Methods

This is a cross-sectional study conducted among 550 female students in six universities across Lebanon. The prevalence of PD, associated risk factors, and management-seeking practices were assessed using a self-administered questionnaire.

Results

The prevalence of PD was 80.9%. Most of the females with PD described their menstrual pain as moderate (56%) to severe (34.6%), which significantly affected their daily activities and studying ability (P < 0.001). The major risk factors associated with PD included heavy menstrual flow (adjusted odds ratio [AOR] = 10.28), family history of PD (AOR = 2.52), history of weight loss attempt (AOR = 2.05), and medical specialization (AOR = 1.663). Only 36.9% of females with PD sought formal medical advice. Most dysmenorrheic females (76.4%) received medications for the management of PD, and remarkably none of them took hormonal contraceptives. Drugs commonly used for PD were mefenamic acid (26.2%), ibuprofen (25%), and paracetamol (11.5%), which were administered when the pain started (58.2%). All medications were significantly effective in reducing the pain score (P = 0.001), and most NSAIDs were more potent than paracetamol in managing PD (P = 0.001). However, no significant difference in adverse effects among medications was revealed. Moreover, no superiority of any individual NSAID for pain relief was established. Nevertheless, mefenamic acid was associated with the lowest risk of abdominal pain (OR: 0.03, P = 0.005) and the highest risk of flank pain (OR = 12, P = 0.02).

Conclusions

Suboptimal management of PD is practiced among university students in Lebanon. Therefore, health care providers should educate dysmenorrheic females to optimize the self-management support of PD. Furthermore, future research is required to investigate females’ misconceptions about hormonal contraceptives in the management of PD, aiming to raise awareness and correct misconceptions.
Restoration of 5-methoxytryptophan protects against atherosclerotic chondrogenesis and calcification in ApoE−/− mice fed high fat diet
Authors: Lee Guan-Lin , Liao Tsai-Lien , Wu Jing-Yiing , Wu Kenneth K. , Kuo Cheng-Chin
Published: November 2021

Background

Toll-like receptor-2 (TLR2) promotes vascular smooth muscle cell (VSMC) transdifferentiation to chondrocytes and calcification in a p38 MAPK-dependent manner. Vascular 5-methoxytryptophan (5-MTP) is a newly identified factor with anti-inflammatory actions. As 5-MTP targets p38 MAPK for its actions, we postulated that 5-MTP protects against vascular chondrogenesis and calcification.

Methods

High-fat diet-induced advanced atherosclerosis in mice were performed to investigate the effect of 5-MTP on atherosclerotic lesions and calcification. VSMCs were used to determine the role of 5-MTP in VSMC chondrogenic differentiation and calcification. Alizarin red S and Alcian blue staining were used to measure VSMC calcification and chondrogenic differentiation, respectively.

Results

5-MTP was detected in aortic tissues of ApoE−/− mice fed control chow. It was reduced in ApoE−/− mice fed high-fat diet (HFD), but was restored in ApoE−/−Tlr2−/− mice, suggesting that HFD reduces vascular 5-MTP production via TLR2. Intraperitoneal injection of 5-MTP or its analog into ApoE−/− mice fed HFD reduced aortic atherosclerotic lesions and calcification which was accompanied by reduction of chondrogenesis and calcium deposition. Pam3CSK4 (Pam3), ligand of TLR2, induced SMC phenotypic switch to chondrocytes. Pretreatment with 5-MTP preserved SMC contractile proteins and blocked Pam3-induced chondrocyte differentiation and calcification. 5-MTP inhibited HFD-induced p38 MAPK activation in vivo and Pam3-induced p38 MAPK activation in SMCs. 5-MTP suppressed HFD-induced CREB activation in aortic tissues and Pam3-induced CREB and NF-κB activation in SMCs.

Conclusions

These findings suggest that 5-MTP is a vascular arsenal against atherosclerosis and calcification by inhibiting TLR2–mediated SMC phenotypic switch to chondrocytes and the consequent calcification. 5-MTP exerts these effects by blocking p38 MAPK activation and inhibiting CREB and NF-κB transactivation activity.
Socioeconomic gradient in COVID-19 vaccination: evidence from Israel
Authors: Saban Mor , Myers Vicki , Ben-Shetrit Shani , Wilf-Miron Rachel
Published: November 2021

Background

Low socioeconomic status (SES) groups have been disproportionately affected by the COVID-19 pandemic. We aimed to examine COVID-19 vaccination rate by neighborhood SES and ethnicity in Israel, a country which has achieved high vaccination rates.

Methods

Data on vaccinations were obtained from the Israeli Ministry of Health’s open COVID-19 database, for December 20, 2020 to August 31, 2021. Correlation between vaccination rate and neighborhood SES was analyzed. Difference in vaccination rate between the first and second vaccine dose was analyzed by neighborhood SES and ethnicity.

Findings

A clear socioeconomic gradient was demonstrated, with higher vaccination rates in the higher SES categories (first dose: r = 0.66; second dose: r = 0.74; third dose: r = 0.92). Vaccination uptake was lower in the lower SES groups and in the Arab population, with the largest difference in uptake between Jewish and Arab localities for people younger than 60, and with the gap widening between first and third doses.

Conclusions

Low SES groups and the Arab ethnic minority demonstrated disparities in vaccine uptake, which were greater for the second and third, compared with the first vaccine dose. Strategies to address vaccination inequity will need to identify barriers, provide targeted information, and include trust-building in disadvantaged communities.
Women’s experiences of accessing individualized disability supports: gender inequality and Australia’s National Disability Insurance Scheme
Authors: Yates Sophie , Carey Gemma , Hargrave Jen , Malbon Eleanor , Green Celia
Published: November 2021

Background

Care services in industrialized nations are increasingly moving towards individualized funding models, which aim to increase individuals’ flexibility, choice and control over their services and supports. Recent research suggests that such schemes have the potential to exacerbate inequalities, however none has explored gendered dimensions of inequality. The Australian National Disability Insurance Scheme (NDIS) is a major individualized funding reform, and has a female participation rate of only 37%, despite women and girls making up half of the disability population.

Methods

The objective of the study is to explore possible gendered barriers to applying for and receiving adequate support through the NDIS, and to suggest directions for future research. We report on semi-structured interviews with 30 women with disability and explore their experiences with the NDIS and their perspectives on challenges associated with being a woman seeking disability support in Australia. We analyse the results using thematic analysis.

Results

Most women in our sample reported differences between the experiences of men and women seeking disability support in Australia. Commonly reported gendered barriers to women being able to access the right supports for their disability involve a) confidence, negotiation and self-advocacy, b) gendered discrimination in diagnosis and the medical system, which has implications for disability support access, and c) support for and recognition of caring roles.

Conclusions

These results suggest that women are not receiving equitable treatment with regard to the NDIS, and that further research and policy reform are needed to ensure that women with disability are not further disadvantaged as a result of the move toward individualized funding models.
Occupational factors and miscarriages in the US fire service: a cross-sectional analysis of women firefighters
Authors: Jung Alesia M. , Jahnke Sara A. , Dennis Leslie K. , Bell Melanie L. , Burgess Jefferey L. , Jitnarin Nattinee , Kaipust Christopher M. , Farland Leslie V.
Published: November 2021

Background

Evidence from previous studies suggests that women firefighters have greater risk of some adverse reproductive outcomes. The purpose of this study was to investigate whether women firefighters had greater risk of miscarriage compared to non-firefighters and whether there were occupational factors associated with risk of miscarriage among firefighters.

Methods

We studied pregnancies in the United States fire service using data from the Health and Wellness of Women Firefighters Study (n = 3181). We compared the prevalence of miscarriage among firefighters to published rates among non-firefighters using age-standardized prevalence ratios. We used generalized estimating equations to estimate relative risks (RRs) and 95% confidence intervals (CIs) between occupational factors (employment (career/volunteer), wildland firefighter status (wildland or wildland-urban-interface/structural), shift schedule, fire/rescue calls at pregnancy start) and risk of miscarriage, adjusted for age at pregnancy, education, gravidity, BMI, and smoking. We evaluated if associations varied by age at pregnancy or employment.

Results

Among 1074 firefighters and 1864 total pregnancies, 404 pregnancies resulted in miscarriages (22%). Among most recent pregnancies, 138 resulted in miscarriage (13%). Compared to a study of US nurses, firefighters had 2.33 times greater age-standardized prevalence of miscarriage (95% CI 1.96–2.75). Overall, we observed that volunteer firefighters had an increased risk of miscarriage which varied by wildland status (interaction p-value< 0.01). Among structural firefighters, volunteer firefighters had 1.42 times the risk of miscarriage (95% CI 1.11–1.80) compared to career firefighters. Among wildland/wildland-urban-interface firefighters, volunteer firefighters had 2.53 times the risk of miscarriage (95% CI 1.35–4.78) compared to career firefighters.

Conclusions

Age-standardized miscarriage prevalence among firefighters may be greater than non-firefighters and there may be variation in risk of miscarriage by fire service role. Further research is needed to clarify these associations to inform policy and decision-making.
Drug triggered pruritus, rash, papules, and blisters – is AGEP a clash of an altered sphingolipid-metabolism and lysosomotropism of drugs accumulating in the skin?
Authors: Blaess Markus , Kaiser Lars , Sommerfeld Oliver , Csuk René , Deigner Hans-Peter
Published: November 2021

Rash, photosensitivity, erythema multiforme, and the acute generalized exanthematous pustulosis (AGEP) are relatively uncommon adverse reactions of drugs. To date, the etiology is not well understood and individual susceptibility still remains unknown. Amiodarone, chlorpromazine, amitriptyline, and trimipramine are classified lysosomotropic as well as photosensitizing, however, they fail to trigger rash and pruritic papules in all individuals. Lysosomotropism is a common charcteristic of various drugs, but independent of individuals. There is evidence that the individual ability to respond to external oxidative stress is crosslinked with the elongation of long-chain fatty acids to very long-chain fatty acids by ELOVLs. ELOVL6 and ELOVL7 are sensitive to ROS induced depletion of cellular NADPH and insufficient regeneration via the pentose phosphate pathway and mitochondrial fatty acid oxidation. Deficiency of NADPH in presence of lysosomotropic drugs promotes the synthesis of C16-ceramide in lysosomes and may contribute to emerging pruritic papules of AGEP. However, independently from a lysosomomotropic drug, severe depletion of ATP and NAD(P)H, e.g., by UV radiation or a potent photosensitizer can trigger likewise the collapse of the lysosomal transmembrane proton gradient resulting in lysosomal C16-ceramide synthesis and pruritic papules. This kind of papules are equally present in polymorphous light eruption (PMLE/PLE) and acne aestivalis (Mallorca acne). The suggested model of a compartmentalized ceramide metabolism provides a more sophisticated explanation of cutaneous drug adverse effects and the individual sensitivity to UV radiation. Parameters such as pKa and ClogP of the triggering drug, cutaneous fatty acid profile, and ceramide profile enables new concepts in risk assessment and scoring of AGEP as well as prophylaxis outcome.
Self-amplification of oxidative stress with tumour microenvironment-activatable iron-doped nanoplatform for targeting hepatocellular carcinoma synergistic cascade therapy and diagnosis
Authors: Zhou Qiao-Mei , Lu Yuan-Fei , Zhou Jia-Ping , Yang Xiao-Yan , Wang Xiao-Jie , Yu Jie-Ni , Du Yong-Zhong , Yu Ri-Sheng
Published: November 2021

Background

Hepatocellular carcinoma is insensitive to many chemotherapeutic agents. Ferroptosis is a form of programmed cell death with a Fenton reaction mechanism. It converts endogenous hydrogen peroxide into highly toxic hydroxyl radicals, which inhibit hepatocellular carcinoma progression.

Methods

The morphology, elemental composition, and tumour microenvironment responses of various organic/inorganic nanoplatforms were characterised by different analytical methods. Their in vivo and in vitro tumour-targeting efficacy and imaging capability were analysed by magnetic resonance imaging. Confocal microscopy, flow cytometry, and western blotting were used to investigate the therapeutic efficacy and mechanisms of complementary ferroptosis/apoptosis mediated by the nanoplatforms.

Results

The nanoplatform consisted of a silica shell doped with iron and disulphide bonds and an etched core loaded with doxorubicin that generates hydrogen peroxide in situ and enhances ferroptosis. It relied upon transferrin for targeted drug delivery and could be activated by the tumour microenvironment. Glutathione-responsive biodegradability could operate synergistically with the therapeutic interaction between doxorubicin and iron and induce tumour cell death through complementary ferroptosis and apoptosis. The nanoplatform also has a superparamagnetic framework that could serve to guide and monitor treatment under T2-weighted magnetic resonance imaging.

Conclusion

This rationally designed nanoplatform is expected to integrate cancer diagnosis, treatment, and monitoring and provide a novel clinical antitumour therapeutic strategy.

Graphical Abstract
Theoretically informed gender analysis for gambling harm reduction: a New Zealand study
Authors: Palmer du Preez Katie , Paavonen Anna-Marie , Bellringer Maria E.
Published: November 2021

Background

Gambling harm affects men and women relatively equally, and gender influences the social determinants of gambling harm. Responses to preventing and minimising women’s gambling harm have been shaped and constrained by population research identifying male gender as a key risk factor for gambling problems. Gender analysis in gambling studies is rare and has lacked theoretical underpinning and coherence, limiting possibilities for gender-responsive and gender-aware harm prevention and reduction activities.

Methods

Two influential qualitative studies of gambling harm in New Zealand (involving total n = 165 people who gambled, affected others, community leaders, gambling and community support service providers, policy makers and academics) neglected to explore the role of gender. This study revisited data collected in these studies, using thematic analysis informed by feminist social constructionist theory. The overarching research questions were: How do gender-related issues, notions and practices influence women’s gambling related harm? What are the implications for women’s gambling harm reduction?

Results

Women’s socio-cultural positioning as primary caregivers for families and children constrained their ability to access a range of recreational and support options and increased the attractiveness of local gambling opportunities as accessible and ‘safe’ outlets for stress reduction. Patriarchal practices of power and control within family contexts operated to maintain gambling behaviour, shut down alternative recreational opportunities, and limit women’s autonomy. Consideration of these themes in relation to current health promotion practice in New Zealand revealed that national programmes and strategies appear to be operating without cognisance of these gender dynamics and therefore have the potential to exacerbate or cause some women harm.

Conclusions

This study demonstrates the value of theoretically informed gender analysis for gambling harm reduction research, policy and practice. International guidelines for gender-aware and gender-responsive health research and practice should be engaged as a foundation for strategic and effective gambling harm reduction programmes, projects, research and policy, and as an essential part of developing and implementing interventions for gambling harm.
Superior vena cava syndrome after pacemaker implantation treated with direct oral anticoagulation
Authors: Mumoli Nicola , Mazzone Antonino , Evangelista Isabella , Cei Marco , Colombo Alessandra
Published: November 2021

Background

Superior Vena Cava (SVC) syndrome, is a quite rare but serious complication after pacemaker lead implantation; most patients are asymptomatic due to the development of adequate venous collateral circulation.

Case presentation

We report a case of a 75-year-old woman who developed SVC syndrome after transvenous pacemaker implantation with complete resolution of the thrombosis after 3 months of oral anticoagulation.

Conclusions

Generally other causes as malignancy are considered to be the most common etiology of SVC syndrome, but benign iatrogenic causes, mainly intravascular devices (central vein catheters, cardiac defibrillators and pacemaker wires), are becoming increasingly common. Procedures performed on venous vasculature, causing a possible intimal injury or vein stenosis, provoked by transvenous leads, seem to be the most reasonable explanation for the observed complication.
The effect of macrophage polarization on the expression of the oxytocin signalling system in enteric neurons
Authors: Shi Yao , Li Shuang , Zhang Haojie , Zhu Jianchun , Che Tongtong , Yan Bing , Li Jingxin , Liu Chuanyong
Published: November 2021

Background

The aim of the current study was to investigate the effect of macrophage polarization on the expression of oxytocin (OT) and the oxytocin receptor (OTR) in enteric neurons.

Methods

In this study, we used a classic colitis model and D-mannose model to observe the correlation between macrophage polarization and OT signalling system. In order to further demonstrate the effect of macrophages, we examined the expression of OT signalling system after depletion of macrophages.

Results

The data showed that, in vitro, following polarization of macrophages to the M1 type by LPS, the macrophage supernatant contained proinflammatory cytokines (IL-1β, IL-6 and TNF-α) that inhibited the expression of OT and OTR in cultured enteric neurons; following macrophage polarization to the M2 type by IL4, the macrophage supernatant contained anti-inflammatory cytokines (TGF-β) that promoted the expression of OT and OTR in cultured enteric neurons. Furthermore, M1 macrophages decreased the expression of the OT signalling system mainly through STAT3/NF-κB pathways in cultured enteric neurons; M2 macrophages increased the expression of the OT signalling system mainly through activation of Smad2/3 and inhibition of the expression of Peg3 in cultured enteric neurons. In a colitis model, we demonstrated that macrophages were polarized to the M1 type during the inflammatory phase, with significant decreased in the expression of OT and OTR. When macrophages were polarized to the M2 type during the recovery phase, OT and OTR expression increased significantly. In addition, we found that D-mannose increased the expression of OT and OTR through polarization of macrophages to the M2 type.

Conclusions

This is the first study to demonstrate that macrophage polarization differentially regulates the expression of OT and OTR in enteric neurons.
European evidence-based recommendations for clinical assessment of upper limb in neurorehabilitation (CAULIN): data synthesis from systematic reviews, clinical practice guidelines and expert consensus
Authors: Prange-Lasonder Gerdienke B. , Alt Murphy Margit , Lamers Ilse , Hughes Ann-Marie , Buurke Jaap H. , Feys Peter , Keller Thierry , Klamroth-Marganska Verena , Tarkka Ina M. , Timmermans Annick , Burridge Jane H.
Published: November 2021

Background

Technology-supported rehabilitation can help alleviate the increasing need for cost-effective rehabilitation of neurological conditions, but use in clinical practice remains limited. Agreement on a core set of reliable, valid and accessible outcome measures to assess rehabilitation outcomes is needed to generate strong evidence about effectiveness of rehabilitation approaches, including technologies. This paper collates and synthesizes a core set from multiple sources; combining existing evidence, clinical practice guidelines and expert consensus into European recommendations for Clinical Assessment of Upper Limb In Neurorehabilitation (CAULIN).

Methods

Data from systematic reviews, clinical practice guidelines and expert consensus (Delphi methodology) were systematically extracted and synthesized using strength of evidence rating criteria, in addition to recommendations on assessment procedures. Three sets were defined: a core set: strong evidence for validity, reliability, responsiveness and clinical utility AND recommended by at least two sources; an extended set: strong evidence OR recommended by at least two sources and a supplementary set: some evidence OR recommended by at least one of the sources.

Results

In total, 12 measures (with primary focus on stroke) were included, encompassing body function and activity level of the International Classification of Functioning and Health. The core set recommended for clinical practice and research: Fugl-Meyer Assessment of Upper Extremity (FMA-UE) and Action Research Arm Test (ARAT); the extended set recommended for clinical practice and/or clinical research: kinematic measures, Box and Block Test (BBT), Chedoke Arm Hand Activity Inventory (CAHAI), Wolf Motor Function Test (WMFT), Nine Hole Peg Test (NHPT) and ABILHAND; the supplementary set recommended for research or specific occasions: Motricity Index (MI); Chedoke-McMaster Stroke Assessment (CMSA), Stroke Rehabilitation Assessment Movement (STREAM), Frenchay Arm Test (FAT), Motor Assessment Scale (MAS) and body-worn movement sensors. Assessments should be conducted at pre-defined regular intervals by trained personnel. Global measures should be applied within 24 h of hospital admission and upper limb specific measures within 1 week.

Conclusions

The CAULIN recommendations for outcome measures and assessment procedures provide a clear, simple, evidence-based three-level structure for upper limb assessment in neurological rehabilitation. Widespread adoption and sustained use will improve quality of clinical practice and facilitate meta-analysis, critical for the advancement of technology-supported neurorehabilitation.
IRFinder-S: a comprehensive suite to discover and explore intron retention
Authors: Lorenzi Claudio , Barriere Sylvain , Arnold Katharina , Luco Reini F. , Oldfield Andrew J. , Ritchie William
Published: November 2021

Accurate quantification and detection of intron retention levels require specialized software. Building on our previous software, we create a suite of tools called IRFinder-S, to analyze and explore intron retention events in multiple samples. Specifically, IRFinder-S allows a better identification of true intron retention events using a convolutional neural network, allows the sharing of intron retention results between labs, integrates a dynamic database to explore and contrast available samples, and provides a tested method to detect differential levels of intron retention.
The p53 family member p73 in the regulation of cell stress response
Authors: Rozenberg Julian M. , Zvereva Svetlana , Dalina Aleksandra , Blatov Igor , Zubarev Ilya , Luppov Daniil , Bessmertnyi Alexander , Romanishin Alexander , Alsoulaiman Lamak , Kumeiko Vadim , Kagansky Alexander , Melino Gerry , Ganini Carlo , Barlev Nikolai A.
Published: November 2021

During oncogenesis, cells become unrestrictedly proliferative thereby altering the tissue homeostasis and resulting in subsequent hyperplasia. This process is paralleled by resumption of cell cycle, aberrant DNA repair and blunting the apoptotic program in response to DNA damage. In most human cancers these processes are associated with malfunctioning of tumor suppressor p53. Intriguingly, in some cases two other members of the p53 family of proteins, transcription factors p63 and p73, can compensate for loss of p53. Although both p63 and p73 can bind the same DNA sequences as p53 and their transcriptionally active isoforms are able to regulate the expression of p53-dependent genes, the strongest overlap with p53 functions was detected for p73. Surprisingly, unlike p53, the p73 is rarely lost or mutated in cancers. On the contrary, its inactive isoforms are often overexpressed in cancer. In this review, we discuss several lines of evidence that cancer cells develop various mechanisms to repress p73-mediated cell death. Moreover, p73 isoforms may promote cancer growth by enhancing an anti-oxidative response, the Warburg effect and by repressing senescence. Thus, we speculate that the role of p73 in tumorigenesis can be ambivalent and hence, requires new therapeutic strategies that would specifically repress the oncogenic functions of p73, while keeping its tumor suppressive properties intact.
Which assessments are used to analyze neuromuscular control by electromyography after an anterior cruciate ligament injury to determine readiness to return to sports? A systematic review
Authors: Blasimann Angela , Koenig Irene , Baert Isabel , Baur Heiner , Vissers Dirk
Published: November 2021

Background

Adequate neuromuscular control of the knee could be one element to prevent secondary injuries after an anterior cruciate ligament (ACL) injury. To assess neuromuscular control in terms of time, amplitude and activity, electromyography (EMG) is used. However, it is unclear which assessments using EMG could be used for a safe return to sports (RTS). Therefore, we aimed to summarize EMG-related assessments for neuromuscular control of the knee in adult patients after an ACL injury to decide upon readiness for RTS.

Methods

This systematic review followed guidelines of Preferred Reporting of Items for Systematic Reviews and Meta-Analyses (PRISMA) and Cochrane recommendations. MEDLINE/PubMed, EMBASE, CINAHL, Cochrane Library, Physiotherapy Evidence Database (PEDro), SPORTDiscus and the Web of Science were searched from inception to March 2019 and updated in November 2020. Studies identifying electromyographic assessments for neuromuscular control during dynamic tasks in adult, physically active patients with an anterior cruciate ligament injury were eligible and qualitatively synthesized. Two independent reviewers used a modified Downs and Black checklist to assess risk of bias of included studies.

Results

From initially 1388 hits, 38 mainly cross-sectional, case-controlled studies were included for qualitative analysis. Most studies provided EMG outcomes of thigh muscles during jumping, running or squatting. Outcomes measures described neuromuscular control of the knee in domains of time, amplitude or activity. Risk of bias was medium to high due to an unclear description of participants and prior interventions, confounding factors and incompletely reported results.

Conclusions

Despite a wide range of EMG outcome measures for neuromuscular control, none was used to decide upon return to sports in these patients. Additional studies are needed to define readiness towards RTS by assessing neuromuscular control in adult ACL patients with EMG. Further research should aim at finding reliable and valid, EMG-related variables to be used as diagnostic tool for neuromuscular control. Moreover, future studies should aim at more homogenous groups including adequately matched healthy subjects, evaluate gender separately and use sport-specific tasks.

Registration The protocol for this systematic review was indexed beforehand in the International Prospective Register of Systematic Reviews (PROSPERO) and registered as CRD42019122188.
N-Methyl-D-aspartate (NMDA) and cannabinoid CB2 receptors form functional complexes in cells of the central nervous system: insights into the therapeutic potential of neuronal and microglial NMDA receptors
Authors: Rivas-Santisteban Rafael , Lillo Alejandro , Lillo Jaume , Rebassa Joan-Biel , Contestí Joan S. , Saura Carlos A. , Franco Rafael , Navarro Gemma
Published: November 2021

Background

The cannabinoid CB2 receptor (CB2R), which is a target to afford neuroprotection, and N-methyl-D-aspartate (NMDA) ionotropic glutamate receptors, which are key in mediating excitatory neurotransmission, are expressed in both neurons and glia. As NMDA receptors are the target of current medication in Alzheimer’s disease patients and with the aim of finding neuromodulators of their actions that could provide benefits in dementia, we hypothesized that cannabinoids could modulate NMDA function.

Methods

Immunocytochemistry was used to analyze the colocalization between CB2 and NMDA receptors; bioluminescence resonance energy transfer was used to detect CB2-NMDA receptor complexes. Calcium and cAMP determination, mitogen-activated protein kinase (MAPK) pathway activation, and label-free assays were performed to characterize signaling in homologous and heterologous systems. Proximity ligation assays were used to quantify CB2-NMDA heteromer expression in mouse primary cultures and in the brain of APPSw/Ind transgenic mice, an Alzheimer’s disease model expressing the Indiana and Swedish mutated version of the human amyloid precursor protein (APP).

Results

In a heterologous system, we identified CB2-NMDA complexes with a particular heteromer print consisting of impairment by cannabinoids of NMDA receptor function. The print was detected in activated primary microglia treated with lipopolysaccharide and interferon-γ. CB2R activation blunted NMDA receptor-mediated signaling in primary hippocampal neurons from APPSw/Ind mice. Furthermore, imaging studies showed that in brain slices and in primary cells (microglia or neurons) from APPSw/Ind mice, there was a marked overexpression of macromolecular CB2-NMDA receptor complexes thus becoming a tool to modulate excessive glutamate input by cannabinoids.

Conclusions

The results indicate a negative cross-talk in CB2-NMDA complexes signaling. The expression of the CB2-NMDA receptor heteromers increases in both microglia and neurons from the APPSw/Ind transgenic mice, compared with levels in samples from age-matched control mice.
How does DICOM support big data management? Investigating its use in medical imaging community
Authors: Aiello Marco , Esposito Giuseppina , Pagliari Giulio , Borrelli Pasquale , Brancato Valentina , Salvatore Marco
Published: November 2021

The diagnostic imaging field is experiencing considerable growth, followed by increasing production of massive amounts of data. The lack of standardization and privacy concerns are considered the main barriers to big data capitalization. This work aims to verify whether the advanced features of the DICOM standard, beyond imaging data storage, are effectively used in research practice. This issue will be analyzed by investigating the publicly shared medical imaging databases and assessing how much the most common medical imaging software tools support DICOM in all its potential. Therefore, 100 public databases and ten medical imaging software tools were selected and examined using a systematic approach. In particular, the DICOM fields related to privacy, segmentation and reporting have been assessed in the selected database; software tools have been evaluated for reading and writing the same DICOM fields. From our analysis, less than a third of the databases examined use the DICOM format to record meaningful information to manage the images. Regarding software, the vast majority does not allow the management, reading and writing of some or all the DICOM fields. Surprisingly, if we observe chest computed tomography data sharing to address the COVID-19 emergency, there are only two datasets out of 12 released in DICOM format. Our work shows how the DICOM can potentially fully support big data management; however, further efforts are still needed from the scientific and technological community to promote the use of the existing standard, encouraging data sharing and interoperability for a concrete development of big data analytics.
Sex differences in the expression of the endocannabinoid system within V1M cortex and PAG of Sprague Dawley rats
Authors: Levine Aidan , Liktor-Busa Erika , Lipinski Austin A. , Couture Sarah , Balasubramanian Shreya , Aicher Sue A. , Langlais Paul R. , Vanderah Todd W. , Largent-Milnes Tally M.
Published: November 2021

Background

Several chronic pain disorders, such as migraine and fibromyalgia, have an increased prevalence in the female population. The underlying mechanisms of this sex-biased prevalence have yet to be thoroughly documented, but could be related to endogenous differences in neuromodulators in pain networks, including the endocannabinoid system. The cellular endocannabinoid system comprises the endogenous lipid signals 2-AG (2-arachidonoylglycerol) and AEA (anandamide); the enzymes that synthesize and degrade them; and the cannabinoid receptors. The relative prevalence of different components of the endocannabinoid system in specific brain regions may alter responses to endogenous and exogenous ligands.

Methods

Brain tissue from naïve male and estrous staged female Sprague Dawley rats was harvested from V1M cortex, periaqueductal gray, trigeminal nerve, and trigeminal nucleus caudalis. Tissue was analyzed for relative levels of endocannabinoid enzymes, ligands, and receptors via mass spectrometry, unlabeled quantitative proteomic analysis, and immunohistochemistry.

Results

Mass spectrometry revealed significant differences in 2-AG and AEA concentrations between males and females, as well as between female estrous cycle stages. Specifically, 2-AG concentration was lower within female PAG as compared to male PAG (*p = 0.0077); female 2-AG concentration within the PAG did not demonstrate estrous stage dependence. Immunohistochemistry followed by proteomics confirmed the prevalence of 2-AG-endocannabinoid system enzymes in the female PAG.

Conclusions

Our results suggest that sex differences exist in the endocannabinoid system in two CNS regions relevant to cortical spreading depression (V1M cortex) and descending modulatory networks in pain/anxiety (PAG). These basal differences in endogenous endocannabinoid mechanisms may facilitate the development of chronic pain conditions and may also underlie sex differences in response to therapeutic intervention.
Association between preoperative serum homocysteine and delayed neurocognitive recovery after non-cardiac surgery in elderly patients: a prospective observational study
Authors: Zhang Zhen-Feng , Sun Qing-Chun , Xu Yi-Fan , Ding Ke , Dong Meng-Meng , Han Liu , Abdul-Mannan  , Han Yuan , Cao Jun-Li
Published: November 2021

Background

Homocysteine, folate, and vitamin B12involved in 1-carbon metabolism are associated with cognitive disorders. We sought to investigate the relationships between these factors and delayed neurocognitive recovery (dNCR) after non-cardiac surgery.

Methods

This was a prospective observational study of patients (n= 175) who were ≥ 60 years of age undergoing non-cardiac surgery. Patients were evaluated preoperatively and for 1 week postoperatively by using neuropsychological tests and were divided into dNCR or non-dNCR groups according to aZ-score ≤ − 1.96 on at least two of the tests. The relationship between the occurrence of dNCR and preoperative levels of homocysteine, folate, and vitamin B12was analyzed. Univariate and multivariable logistic regression analyses were conducted to identify factors associated with dNCR.

Results

Delayed neurocognitive recovery was observed in 36 of 175 patients (20.6%; 95% confidence interval [CI], 14.5–26.6%) 1 week postoperatively. Patients who developed dNCR had significantly higher median [interquartile range (IQR)] homocysteine concentrations (12.8 [10.9,14.4] μmol/L vs 10.6 [8.6,14.7] μmol/L;P= 0.02) and lower folate concentrations (5.3 [4.2,7.3] ng/mL vs 6.9 [5.3,9.5] ng/mL;P= 0.01) than those without dNCR. Compared to the lowest tertile, the highest homocysteine tertile predicted dNCR onset (odds ratio [OR], 3.9; 95% CI, 1. 3 to 11.6;P= 0.02), even after adjusting for age, sex, education, and baseline Mini Mental State Examination.

Conclusions

Elderly patients with high homocysteine levels who underwent general anesthesia for non-cardiac surgery have an increased risk of dNCR. This knowledge could potentially assist in the development of preventative and/or therapeutic measures.

Trial registration

NCT03084393(https://www.clinicaltrials.gov)
Management of donations of personal protective equipment in response to the massive shortage during the COVID-19 health crisis: providing quality equipment to health care workers
Authors: Cambien Guillaume , Guihenneuc Jérémy , Fouassin Xavier , Castel Olivier , Bousseau Anne , Ayraud-Thevenot Sarah
Published: November 2021

Background

In the COVID-19 pandemic context, a massive shortage of personal protective equipment occurred. To increase the available stocks, several countries appealed for donations from individuals or industries. While national and international standards to evaluate personal protective equipment exist, none of the previous research studied how to evaluate personal protective equipment coming from donations to healthcare establishments. Our aim was to evaluate the quality and possible use of the personal protective equipment donations delivered to our health care establishment in order to avoid a shortage and to protect health care workers throughout the COVID-19 crisis.

Methods

Our intervention focused on evaluation of the quality of donations for medical use through creation of a set of assessment criteria and analysis of the economic impact of these donations.

Results

Between 20th March 2020 and 11th May 2020, we received 239 donations including respirators, gloves, coveralls, face masks, gowns, hats, overshoes, alcohol-based hand rubs, face shields, goggles and aprons. A total of 448,666 (86.3%) products out of the 519,618 initially received were validated and distributed in health care units, equivalent to 126 (52.7%) donations out of the 239 received. The budgetary value of the validated donations was 32,872 euros according to the pre COVID-19 prices and 122,178 euros according to the current COVID-19 prices, representing an increase of 371.7%.

Conclusions

By ensuring a constant influx of personal protective equipment and proper stock management, shortages were avoided. Procurement and distribution of controlled and validated personal protective equipment is the key to providing quality care while guaranteeing health care worker safety.