bluuebunny/crossref_metadata_2025 huggingface dataset:
Fossils constrain biogeographical history in a clade of flattened spiders with transcontinental distribution
Authors: Azevedo Guilherme H. F. , Parreiras Júlia S. , Bougie Tierney , Michalik Peter , Wunderlich Jörg , Ramírez Martín J.
Published: September 2021

Aim

Fossil data may be crucial to infer biogeographical history, especially in taxa with tropical trans‐Pacific distributions. Here, we use extinct and extant trochanteriid flattened spiders to test hypotheses that could explain its trans‐Pacific disjunct distribution, including a Boreotropical origin with a North Atlantic dispersal, an African origin with South Atlantic dispersal and an Eurasian origin with Bering Bridge route.

Location

World‐wide.

Taxon

Trochanteriidae, Plator‐Doliomalus‐Vectius (PDV) clade.

Methods

MicroCT was used to collect morphological data from an undescribed Baltic amber fossil. These data were used with additional fossils and extant species in a total‐evidence, tip‐dated phylogenetic analysis. We tested different scenarios using constrained dispersal matrices in a Bayesian approach. An analysis with fossils pruned was also performed to explore how lack of fossil data might impact inferences of biogeographical process.

Results

The phylogenetic analyses allowed us to place the new fossil in the genus Plator. Analyses without fossils suggest an African origin with a dispersal to Asia from India and a South Atlantic dispersal to South America. When fossils are included, hypothesis‐testing rejects this scenario and equally supports a Boreotropical and an Afro‐European origin with a South Atlantic route and a dispersal to Asia from Europe.

Main conclusions

Biogeographical inferences of disjunctly distributed taxa should be interpreted with caution when fossils are not included. Although one alternative hypothesis was not completely rejected, results show that the Boreotropical hypothesis for the PDV clade could be a robust explanation for its actual distribution. This hypothesis is mostly overlooked in animal taxa and rigorous tests with other taxa with similar distributions may reveal that a Boreotropical origin is common. We discuss methodological approaches that could improve biogeographical tests using fossils as terminals.
Osteogenic and angiogenic profiles of the palatal process of the maxilla and the palatal process of the palatine bone
Authors: Liao Caiyu , Lu Meng , Hong Yuhang , Mao Chuanqing , Chen Jiangping , Ren Chengyan , Lin Minkui , Chen Weihui
Published: September 2021

Hard palate consists anteriorly of the palatal process of the maxilla (ppmx) and posteriorly of the palatal process of the palatine (ppp). Currently, palatal osteogenesis is receiving increasing attention. This is the first study to provide an overview of the osteogenesis process of the mouse hard palate. We found that the period in which avascular mesenchymal condensation becomes a vascularized bone structure corresponds to embryonic day (E) 14.5 to E16.5 in the hard palate. The ppmx and ppp differ remarkably in morphology and molecular respects during osteogenesis. Osteoclasts in the ppmx and ppp are heterogeneous. There was a multinucleated giant osteoclast on the bone surface at the lateral‐nasal side of the ppmx, while osteoclasts in the ppp were more abundant and adjacent to blood vessels but were smaller and had fewer nuclei. In addition, bone remodeling in the hard palate was asymmetric and exclusively occurred on the nasal side of the hard palate at E18.5. During angiogenesis, CD31‐positive endothelial cells were initially localized in the surrounding of palatal mesenchymal condensation and then invaded the condensation in a sprouting fashion. At the transcriptome level, we found 78 differentially expressed genes related to osteogenesis and angiogenesis between the ppmx and ppp. Fifty‐five related genes were up/downregulated from E14.5 to E16.5. Here, we described the morphogenesis and the heterogeneity in the osteogenic and angiogenic genes profiles of the ppmx and ppp, which are significant for subsequent studies of normal and abnormal subjects.
Untargeted LC‐MS‐based metabonomic analysis of the effect of photoperiod on the testes of broiler roosters
Authors: Guo Lewei , Zhu Qingyu , Liu Hongyu , Zhao Jing , Lu Wenfa , Wang Jun
Published: September 2021

Photoperiod is an important factor that stimulates the reproductive performance of broiler breeder roosters. However, the mechanism by which photoperiod affects the reproductive performance of broiler breeder roosters has not been fully studied. To study the effects of different photoperiods on the reproductive performance of broiler breeder roosters, 120 Arbor Acres broiler breeder roosters aged 20 weeks were randomly assigned to three groups (n = 40), and the three groups were treated with different photoperiod regimes: control (CTR; 12.5 h of light and 11.5 h of dark, 12.5 L: 11.5 D), short day (SD; 16 L: 8 D) and long day (LD; 8 L: 16 D). Serum and testes were collected after 4 weeks of feeding, and testosterone‐related indices were detected. We found that testosterone synthesis in the testes of broiler roosters was boosted with prolonged of photoperiod. Subsequently, metabonomics was used to identify the differential endogenous metabolites that may affect the function of the testes in breeder roosters. We found compared with other groups, the concentrations of creatine, uridine monophosphate, phosphoribosyl pyrophosphate, dCMP, α‐D‐glucose and citric acid in the SD group decreased significantly (p < 0.05), and glyoxylic acid, D‐ribose 5‐phosphate, deoxyuridine and orotic acid in the SD group increased significantly (p < 0.05), while the CTR group and LD group showed no significant difference (p > 0.05). The concentrations of linoleic acid and α‐linolenic acid in the LD group were increased significantly (p < 0.05) than those in the CTR and SD groups. Compared with the CTR group, the concentrations of histamine in the SD and LD groups were significant increased (p < 0.05). The 13 of the different metabolites could be used as candidate biomarkers for different photoperiods affecting testosterone synthesis, may be used to molecular breeding of high reproductive performance broiler roosters.
Vulvar vitiligo and lichen sclerosus in children: A clinical challenge
Authors: Veronesi Giulia , Virdi Annalucia , Leuzzi Miriam , Gurioli Carlotta , Chessa Marco Adriano , Guglielmo Alba , Neri Iria
Published: September 2021

Vulvar vitiligo (VV) and vulvar lichen sclerosus (VLS), both feature skin and mucosal hypo‐/depigmentation. The aim of this study was to describe the clinical and dermoscopic features of VV and VLS in the pediatric population, providing diagnostic clues, and to define their association. We performed a systematic literature review of the clinical and dermoscopic features of pediatric VV and VLS. An observational study was conducted on children affected by VLS associated with VV, referred to the Dermatology Unit of the Sant’Orsola Polyclinic in Bologna, Italy. Medical history, age at diagnosis, ethnicity, clinical and dermoscopic features, and symptoms were recorded for all patients. 124 cases of VLS and 10 cases of VV were reviewed. Clinical manifestations included hypo‐/depigmented patches in both conditions, while ecchymosis/purpura and fissures/erosion were observed in VLS. Symptoms including pruritus, pain, or burning were reported only by VLS patients. In our study five patients with VLS associated with VV were retrieved. Clinical features included well‐demarcated depigmented patches in VV and translucent areas, erythema, ecchymoses/purpura, and labial fusion in VLS. Dermoscopy showed white structureless areas with a whipped cream‐like appearance, linear or dotted vessels, white chrysalis‐like structures, erosion and red‐purpuric blotches in VLS and reduced pigment network or pigment absence, intralesional spots of residual pigmentation and telangiectasias in VV. Symptoms were present in all patients. Both VV and VLS show hypo‐/depigmented patches. In the presence of associated symptoms, possible VLS should be investigated with clinical and dermoscopic examination to achieve a prompt diagnosis.
Age‐ and sex‐mediated differences in T lymphocyte populations of kidney transplant recipients
Authors: Dziarmaga Robert , Ke Danbing , Sapir‐Pichhadze Ruth , Cardinal Héloïse , Phan Véronique , Piccirillo Ciriaco A. , Mazer Bruce , Foster Bethany J.
Published: September 2021

Background

Graft failure rates increase through childhood and adolescence, decline in adulthood, and are higher in female than male kidney transplant recipients (KTR) until middle age. We aimed to describe age‐ and sex‐related differences in T‐cell subsets among KTR to determine which differences may help to explain the differences in kidney graft failure rates.

Methods

Effector T (Teff)‐cell and regulatory T (Treg)‐cell phenotypes in PBMCs from healthy controls and KTR, who were at least 1 year post‐transplant with stable graft function under immunosuppression, were analyzed by flow cytometry. The effects of age, sex, and status (KTR or control) were analyzed using linear regressions.

Results

We enrolled 20 male and 21 female KTR and 20 male and 20 female controls between 3 and 29 years of age. CD3+ T‐cell frequencies were not associated with age or sex but were higher in KTR than controls. There were no differences in CD4+ and CD8+ frequencies. Th1 (IFNγ+ IL‐4− IL‐17A−) and Th17 (IL‐17A+) frequencies within the CD4+ T‐cell population were higher at older ages. The frequencies of FOXP3 + Helios + Treg cells in CD4+ CD25+ CD127− T cells were lower in females than males and in KTR than controls.

Conclusions

Increasing frequencies of Th1 and Th17 cells with increasing age mirrors the increasing graft failure rates from childhood to young adulthood. Importantly, sex differences in frequencies of circulating Treg cells may suggest a role in the sex differences in graft failure rates.
A 250‐kDa glycoprotein of Naegleria fowleri induces protection and modifies the expression of α4β1 and LFA‐1 on T and B lymphocytes in mouse meningitis model
Authors: Castillo‐Ramírez Diego A. , Carrasco‐Yépez María Maricela , Rodríguez‐Mera Itzel Berenice , Reséndiz‐Albor Aldo Arturo , Rosales‐Cruz Érica , Rojas‐Hernández Saúl
Published: September 2021

The aims of this work were to evaluate the protective role of the 250‐kDa polypeptide band of Naegleria fowleri. We designed an immunization strategy in Balb/c mice which were inoculated by i.n. route with an electrocuted 250‐kDa polypeptide band of N. fowleri. We observed that the 250‐kDa band induced 80% of protection, whereas the coadministration with Cholera Toxin induced 100% of protection. Moreover, high levels of IgA‐ and IgG‐specific antibodies were detected by ELISA assay. We also analysed migration molecules (α4β1 and LFA‐1) on T and B lymphocytes in nose‐associated lymphoid tissue (NALT), cervical lymph nodes (CN) and nasal passages (NP) by flow cytometry. We observed that the percentage of B cells (B220/α4β1) and T cells (CD4/α4β1) in NP were higher in all immunized groups compared with the other compartments analysed. Finally, we detected by immunohistochemistry ICAM‐1 and V‐CAM‐1 in the nasal cavity. The immunization with the 250‐kDa polypeptide band, protect mice against N. fowleri challenge and modifies migration molecules and their ligands.
The effect of gender on intramuscular pressure in patients with chronic exertional compartment syndrome of the lower leg
Authors: Lindorsson Sophia , Rennerfelt Kajsa , Brisby Helena , Zhang Qiuxia
Published: September 2021

This study aimed to compare intramuscular pressure (IMP) in all four compartments of the lower leg between men and women in patients with suspected chronic exertional compartment syndrome (CECS), and to assess possible effects of gender in relation to covariation factors. A consecutive series of patients with exertional leg pain (n = 962, median age 27 years, 56.2% women) underwent IMP measurements between 2009 and 2019. The CECS diagnosis was confirmed (n = 491, 48% women) or ruled out (n = 471, 65% women) based on the patient's history, clinical examination, and IMP measurements. IMP values of the compartments were compared between genders. A multiple linear regression analysis was performed for IMP in the anterior and lateral compartments, where the number of patients was large enough to investigate the possible impact of other factors such as height, age, and duration of pain. Among those with a confirmed CECS diagnosis, one‐minute post‐exercise IMP was significantly lower in women than in men for all four muscle compartments: anterior (median [range] mmHg 44 [24–120] vs. 50 [24–130]), lateral (35 [20–89] vs. 40 [26–106]), deep posterior (31 [25–36] vs. 34 [24–53]), and superficial posterior (32 [27–39] vs. 37 [22–54]). In the multiple regression analysis, gender differences remained significant in the anterior compartment but not the lateral compartment, where only height remained a significant predictor of IMP. Gender should be considered when using cut‐off values for IMP in diagnosing CECS, especially for the anterior compartment.
Through thick and thin?: Young adults’ implicit beliefs about friendship and their reported use of dissolution and maintenance strategies with same‐gender friends
Authors: Santucci Katya , Khullar Thomas H. , Dirks Melanie A.
Published: September 2021

Despite the documented importance of friendship for the well‐being of young adults, there is a paucity of work mapping factors associated with friendship dissolution and maintenance during this developmental period. We examined whether implicit theories of friendships – specifically, growth beliefs (i.e., the belief that friendships can be developed) and destiny beliefs (i.e., the belief that friendships are either meant to work or not) — were associated with endorsement of dissolution and maintenance responses in two types of challenging situations occurring with same‐gender friends. One hundred forty‐five undergraduate students (80 females, Mage = 20.71, SD = 1.46) completed an online questionnaire. Participants read twelve hypothetical situations depicting transgressions by a friend (i.e., violations of friendship expectancies) or conflicts of interest (i.e., differences of needs, desires, or opinions) and reported how likely they would be to engage in strategies reflecting maintaining the friendship or dissolving it, either by ending it completely or diminishing its quality. They also completed a scale assessing implicit theories of friendships. Participants endorsed dissolving the friendship more strongly when the friend had transgressed than in conflicts of interest, whereas maintenance strategies were endorsed more strongly in conflicts than in transgressions. Moreover, higher destiny beliefs were associated with greater endorsement of ending the friendship and weaker endorsement of maintaining it; in contrast, higher growth beliefs were associated with greater endorsement of maintenance. Findings provide new insight into when and why young adults may dissolve or maintain a friendship.
ABO(H) and Lewis blood group substances and disease treatment
Authors: Liu Junting , Wang Deqing
Published: September 2021

Since the early 20th century, scientists have determined that blood group antigens can be inherited. With more and more studies have been devoted to finding the relationship between blood groups and diseases, the relationship of ABO(H) and Lewis blood groups and the development of human diseases have been summarised. In addition, many studies have shown that blood group substances, such as blood group antigen or related antibody, play an important role in disease prevention and treatment. This review focuses on the advances of ABO(H), Lewis blood group substances in the treatment of diseases, which has important significance for the development of novel therapeutic methods.
Urbanisation and the shifting conditions of the state as a territorial‐political community: A study of the geographies of political efficacy
Authors: Luukkonen Juho , Weckroth Mikko , Kemppainen Teemu , Makkonen Teemu , Sirviö Heikki
Published: September 2021

In this paper, we contribute to recent debates on the geographies of discontent by examining the implications of urbanisation on the state as a territorial‐political community in the European context. Building on an Arendtian conception of politics, we argue that the emergence of the “urban” as a dominant spatio‐political imaginary has led to a narrowing of the conditions of politics and political agency within states. The urban imaginary has provoked selective spatio‐political discourses, geopolitical strategies, and policy practices that have resulted in the exclusion of certain social and spatial fractions of society from a shared sense of community and political agency within the state. To demonstrate this point, we empirically analysed the experience of political efficacy in Europe. The results of our analysis show that perceived external political efficacy is weakest in more rural settings and in regions with low GDP and a declining population. Accordingly, we suggest that policy measures ought to be directed against this sort of political alienation and should be used to create a stronger sense of political belonging and community.
Theorising liminal states of health: A spatio‐temporal analysis of undiagnosis and anticipatory diagnosis in the shadow of toxic pollution
Authors: Senanayake Nari
Published: September 2021

This paper demonstrates how greater engagement with liminality – as a concept and lived experience – can expand scholarly conceptualisations of health/disease in contaminated spaces. Drawing on ethnographic fieldwork conducted in Sri Lanka's dry zone between 2013 and 2017, I focus on residents' encounters with chronic kidney disease diagnosis in a region where the causes of illness are uncertain, the consequences of disease are often deadly, and the possibilities of developing sickness in the future are both unpredictable and ever‐present. Specifically, I examine how residents of kidney disease hotspots negotiate various attempts to categorise them as being, or not being, healthy in ways that give rise to experiences of liminality. Building on work in feminist disability studies, I conceptualise “undiagnosis” and “anticipatory diagnosis” as two such liminal states of health that reconfigure medical and social practices in the dry zone. As part of this analysis, I explain why residents are so reluctant to get screened for kidney disease and demonstrate how they strategically mobilise moments of “undiagnosis” to resist patient subjectivities and prolong existing lifeways. I then turn to a discussion of anticipatory diagnosis, which describes the practice of re‐classifying residents of disease hotspots who are not yet sick as embodying the potential to become ill at any time. Frequently deployed by the state, medical practitioners, and non‐dry zone communities, I demonstrate how this practice collapses categories of “at‐risk” and “diseased” in external categorisations of residents' future health status. In short, liminality comes to be embodied through the constant anticipation of disease despite uncertainty about who will actually become sick and why. Tying these experiences together, I elucidate how geography matters to the constitution of liminal states of health and crucially demonstrate how this liminality helps reproduce place attachments as well as forms of geographic differentiation in the shadow of toxic contamination.
Patterns of employment, skills, and tasks within MNEs associated with offshoring
Authors: Eliasson Kent , Hansson Pär , Lindvert Markus
Published: September 2021

We examine the relationship between relative demands for skills, non‐routine, and non‐offshorable tasks in Swedish MNE parents (onshore) and their employment shares in affiliates abroad (offshore). Our estimations suggest that increased employment shares in affiliates abroad (offshore) result in higher relative demand for skills and larger shares of non‐routine tasks performed by employed that are highly educated in the parents at home (onshore). However, we do not find any evidence for that the share of non‐offshorable tasks rises in the parents of Swedish MNEs when employment shares increase in their affiliates overseas. Furthermore, we estimate the relationships between absolute employment onshore (skilled and less‐skilled labour) and employment in affiliates offshore (high‐ and low‐income countries). Increased employment in affiliates in low‐income countries relates negatively to the employment of less‐skilled workers in manufacturing MNE parents (substitute), whereas increased employment in affiliates in high‐income countries correlates positively with the employment of skilled workers in service MNE parents (complement).
Decision-making in Russia’s Foreign Policy Modelling Russia’s Decision-Making with reference to Ukraine and Moldova (2004-2018)
Authors: Zaidi Kristine
Published: September 2021

There is a substantial body of literature on Russian foreign policy; however, the decision-making aspect remains comparatively less explored. The ambition of this research developed in two directions; on a practical level, it contributes to knowledge on Russia’s foreign policy decision-making and, on a conceptual plane, to scholarship by way of theory development, underpinning academic research on decision-making in foreign policy. Russia’s decision-making was first viewed through the prism of the Rational Actor Model and Incrementalism; however, their utility was found to be limited. Blended models also did not figure strongly. Through the prism of author’s proposed model of Strategic Incrementalism and its principles, this research demonstrates that Russia’s foreign-policy decision-making is far from a case of ‘muddling through,’ it retains a long-term purposefulness, and that its incremental decisions are guided by farsightedness. The simplicity and general applicability of the model potentially suggest its broader utility.
Dysbiosis of the gut microbiome impairs mouse skeletal muscle adaptation to exercise
Authors: Valentino Taylor R. , Vechetti Ivan J. , Mobley C. Brooks , Dungan Cory M. , Golden Lesley , Goh Jensen , McCarthy John J.
Published: September 2021

There is emerging evidence of a gut microbiome–skeletal muscle axis. The purpose of this study was to determine if an intact gut microbiome was necessary for skeletal muscle adaptation to exercise. Forty‐two 4‐month‐old female C57BL/6J mice were randomly assigned to untreated (U) or antibiotic‐treated (T) non‐running controls (CU or CT, respectively) or progressive weighted wheel running (PoWeR, P) untreated (PU) or antibiotic‐treated (PT) groups. Antibiotic treatment resulted in disruption of the gut microbiome as indicated by a significant depletion of gut microbiome bacterial species in both CT and PT groups. The training stimulus was the same between PU and PT groups as assessed by weekly (12.35 ± 2.06 vs. 11.09 ± 1.76 km/week, respectively) and total (778.9 ± 130.5 vs. 703.8 ± 112.9 km, respectively) running activity. In response to PoWeR, PT showed less hypertrophy of soleus type 1 and 2a fibres and plantaris type 2b/x fibres compared to PU. The higher satellite cell and myonuclei abundance of PU plantaris muscle after PoWeR was not observed in PT. The fibre‐type shift of PU plantaris muscle to a more oxidative type 2a fibre composition following PoWeR was blunted in PT. There was no difference in serum cytokine levels among all groups suggesting disruption of the gut microbiome did not induce systemic inflammation. The results of this study provide the first evidence that an intact gut microbiome is necessary for skeletal muscle adaptation to exercise.

image

Key points

Dysbiosis of the gut microbiome caused by continuous antibiotic treatment did not affect running activity.

Continuous treatment with antibiotics did not result in systemic inflammation as indicated by serum cytokine levels.

Gut microbiome dysbiosis was associated with blunted fibre type‐specific hypertrophy in the soleus and plantaris muscles in response to progressive weighted wheel running (PoWeR).

Gut microbiome dysbiosis was associated with impaired PoWeR‐induced fibre‐type shift in the plantaris muscle.

Gut microbiome dysbiosis was associated with a loss of PoWeR‐induced myonuclei accretion in the plantaris muscle.
Impact of a National Peer-Led Training Program to Increase Brief Physical Activity Advice Given to Patients by Health Care Professionals
Authors: Carlin Liz , Whelan Maxine E. , Musson Hayley , Adams Emma J.
Published: September 2021

Background: The benefits of physical activity for preventing and managing long-term health conditions are well established and health care professionals could promote physical activity to patients. The current study aims to evaluate the impact of the Clinical Champions Physical Activity Training Program. Methods: Health care professionals attend a one-off in-person training session delivered by a trained Clinical Champion. Attendees at the Clinical Champions Physical Activity Training Program were asked to complete a baseline survey prior to the training session and follow-up surveys 4 and 12 weeks posttraining. Results: A total of 5945 training attendees completed the baseline survey. A total of 1859 and 754 participants completed 4- and 12-week follow-up (31.3% and 12.7% response rate, respectively). Significant increases in confidence to deliver brief physical activity advice and knowledge of physical activity guidelines were reported at 12 weeks (P < .001). The perceived frequency of physical activity discussions with patients significantly increased (P < .001). Twelve weeks after training, fewer barriers in promoting physical activity were reported. Conclusions: The evaluation of the Clinical Champions Physical Activity Training Program demonstrated an increase in knowledge of physical activity guidelines, levels of confidence, and frequency of delivery of brief physical activity advice to patients. Further research is required to determine if this impact translates into changes to patients’ physical activity behavior.
Detection and Characterization of Targeted Carbapenem-Resistant Health Care-Associated Threats: Findings from the Antibiotic Resistance Laboratory Network, 2017 to 2019
Authors: Sabour Sarah , Huang Jennifer Y. , Bhatnagar Amelia , Gilbert Sarah E. , Karlsson Maria , Lonsway David , Lutgring Joseph D. , Rasheed J. Kamile , Halpin Alison Laufer , Stanton Richard A. , Gumbis Stephanie , Elkins Christopher A. , Brown Allison C.
Published: September 2021

Carbapenemase gene-positive (CP) Gram-negative bacilli are of significant clinical and public health concern. Their rapid detection and containment are critical to preventing their spread and additional infections they can cause.
Impact of HIV-1 Resistance-Associated Mutations on Susceptibility to Doravirine: Analysis of Real-World Clinical Isolates
Authors: Asante-Appiah Ernest , Lai Johnny , Wan Hong , Yang Dongmei , Martin Elizabeth Anne , Sklar Peter , Hazuda Daria , Petropoulos Christos J. , Walworth Charles , Grobler Jay A.
Published: September 2021

Clinical management of human immunodeficiency virus type-1 (HIV-1) infection may be negatively impacted by either acquired or transmitted drug resistance. Here, we aim to extend our understanding of the impact of resistance-associated mutations (RAMs) on the susceptibility of clinical isolates to the nonnucleoside reverse transcriptase inhibitor (NNRTI) doravirine. Clinical isolates from people living with HIV-1 undergoing routine testing for susceptibility to doravirine and other approved NNRTIs (etravirine, rilpivirine, efavirenz, and nevirapine) were collected from August 2018 to August 2019. Susceptibility in the presence/absence of NNRTI and nucleos(t)ide reverse transcriptase inhibitor (NRTI) mutations was determined using cutoffs for relative fold change in inhibition (ratio of the 50% inhibitory concentration [IC
50
] of patient virus compared with the IC
50
of a wild-type reference strain). Biological cutoffs of 3- to 15-fold change were investigated for doravirine, with preestablished cutoffs used for the other NNRTIs. Of 4,070 clinical isolates, 42.9% had ≥1 NNRTI RAM. More isolates were susceptible to doravirine (92.5–96.7%) than to etravirine (91.5%), rilpivirine (89.5%), efavirenz (81.5%), or nevirapine (77.5%). Based on a 3-fold cutoff, doravirine susceptibility was retained in 44.7–65.8% of isolates resistant to another NNRTI and 28.5% of isolates resistant to all other tested NNRTIs. The presence of NRTI RAMs including thymidine analog mutations was associated with doravirine hypersusceptibility in some isolates, particularly in the absence of NNRTI RAMs. These results support the favorable resistance profile of doravirine and are of particular importance given the challenge posed by both acquired and transmitted resistance.
Direct and Indirect Interactions Promote Complexes of the Lipoprotein LbcA, the CtpA Protease and Its Substrates, and Other Cell Wall Proteins in Pseudomonas aeruginosa
Authors: Chakraborty Dolonchapa , Darwin Andrew J.
Published: September 2021

Carboxyl-terminal processing proteases (CTPs) are widely conserved and associated with the virulence of several bacteria, including CtpA in
Pseudomonas aeruginosa
. CtpA copurifies with the uncharacterized lipoprotein LbcA.
Understanding complexities in the uptake of indigenously developed rapid point-of-care diagnostics for containment of antimicrobial resistance in India
Authors: Sharma Monica , Gangakhedkar Raman R , Bhattacharya Sanjay , Walia Kamini
Published: September 2021

A good point-of-care diagnostic test holds a promise to reduce inappropriate use of antibiotics by enabling early detection of the pathogen and facilitating rapid testing of antimicrobial susceptibility. India has taken many initiatives in the recent past to augment the development and deployment of diagnostics in Indian health care system. Funding opportunities to promote innovation in diagnostics development were started in early 2000s through various ministries and departments. India released National Essential Diagnostics List which enlists essential tests and there is now Free Diagnostics Service Initiative of Government of India under National Health Mission that mandates to provide all essential tests free of cost. We wanted to understand how these initiatives have impacted the diagnostics that could be of use in containment of antimicrobial resistance (AMR) and whether there is a smooth process for bringing indigenously developed products relevant to AMR into the healthcare system. We conducted a longitudinal survey (January 2019 and January 2021) to understand the availability of market ready indigenous rapid diagnostics for AMR in the country and their progress towards introduction in the private market or uptake in healthcare system. We found that many innovators and developers are working towards development of rapid tests that can be useful in the containment of AMR in India. While there are many promising diagnostics on the horizon, the pathway for uptake of indigenously developed diagnostics in healthcare system remains disjointed and needs to be harmonised for the investments made towards development to translate as tangible gains. Since most of these efforts are government funded, it is incumbent upon the government to also provide a seamless pathway to make these diagnostics available in health care system. In absence of this guidance, most of these diagnostics will sit with the innovators/developers and will never be used for the purpose they were intended to serve.
Protocol for an observational cohort study investigating personalised medicine for intensification of treatment in people with type 2 diabetes mellitus: the PERMIT study
Authors: Bidulka Patrick , O’Neill Stephen , Basu Anirban , Wilkinson Samantha , Silverwood Richard J , Charlton Paul , Briggs Andrew , Adler Amanda I , Khunti Kamlesh , Tomlinson Laurie A , Smeeth Liam , Douglas Ian J , Grieve Richard
Published: September 2021

Introduction

For people with type 2 diabetes mellitus (T2DM) who require an antidiabetic drug as an add-on to metformin, there is controversy about whether newer drug classes such as dipeptidyl peptidase-4 inhibitors (DPP4i) or sodium-glucose co-transporter-2 inhibitors (SGLT2i) reduce the risk of long-term complications compared with sulfonylureas (SU). There is widespread variation across National Health Service Clinical Commissioning Groups (CCGs) in drug choice for second-line treatment in part because National Institute for Health and Care Excellence guidelines do not specify a single preferred drug class, either overall or within specific patient subgroups. This study will evaluate the relative effectiveness of the three most common second-line treatments in the UK (SU, DPP4i and SGLT2i as add-ons to metformin) and help target treatments according to individual risk profiles.

Methods and analysis

The study includes people with T2DM prescribed one of the second-line treatments-of-interest between 2014 and 2020 within the UK Clinical Practice Research Datalink linked with Hospital Episode Statistics and Office of National Statistics. We will use an instrumental variable (IV) method to estimate short-term and long-term relative effectiveness of second-line treatments according to individuals’ risk profiles. This method minimises bias from unmeasured confounders by exploiting the natural variation in second-line prescribing across CCGs as an IV for the choice of prescribed treatment. The primary outcome to assess short-term effectiveness will be change in haemoglobin A1c (%) 12 months after treatment initiation. Outcome measures to assess longer-term effectiveness (maximum ~6 years) will include microvascular and macrovascular complications, all-cause mortality and hospital admissions during follow-up.

Ethics and dissemination

This study was approved by the Independent Scientific Advisory Committee (20-064) and the London School of Hygiene & Tropical Medicine Research Ethics Committee (21395). Results, codelists and other analysis code will be made available to patients, clinicians, policy-makers and researchers.
Association of antenatal corticosteroids with morbidity and mortality among preterm multiple gestations: meta-analysis of observational studies
Authors: Lin Dongxin , Fan Dazhi , Chen Gengdong , Luo Caihong , Guo Xiaoling , Liu Zhengping
Published: September 2021

Objective

This meta-analysis aimed to assess the efficacy of antenatal corticosteroids (ACS) on morbidity and mortality among preterm multiple pregnancies.

Methods

The PubMed, Embase, Web of Science and Cochrane Library databases were searched for studies investigating the outcomes among preterm multiple gestations following to ACS, from their inception to 1 November 2020. Two authors independently performed the study selection, risk of bias assessment and data extraction. The primary outcomes were respiratory distress syndrome (RDS) and mortality and secondary outcomes included intraventricular haemorrhage (IVH), periventricular leukomalacia (PVL), necrotising enterocolitis, retinopathy of prematurity and bronchopulmonary dysplasia. Pooled ORs were obtained using random effects models. Subgroup analyses were performed to explain heterogeneity by ACS completeness, administration-to-delivery intervals (≤7 days) and single or multicentre.

Results

A total of 16 observational studies with 36 973 newborns were included in the meta-analysis. ACS treatment was associated with a reduction in RDS (OR 0.66; 95% CI 0.54 to 0.82; I2=91.4%; p<0.001), mortality (OR 0.64; 95% CI 0.50 to 0.81; I2=85.9%; p<0.001), IVH (OR 0.67; 95% CI 0.54 to 0.83; I2=77.4%; p<0.001) and PVL (OR 0.65; 95% CI 0.47 to 0.92; I2=75.5%; p<0.001). Subgroup analyses showed ACS completeness, administration-to-delivery interval and multicentre study affected these associations.

Discussion

ACS may be beneficial for reducing the risks of RDS, mortality, IVH and PVL among preterm multiple gestations. The efficacy of ACS could be affected by ACS completeness and administration-to-delivery. More robust evidence on the efficacy of ACS treatment among multiple gestations is warranted.
Variation in preoperative stress testing by patient, physician and surgical type: a cohort study
Authors: Pappas Matthew A , Sessler Daniel I , Auerbach Andrew D , Kattan Michael W , Milinovich Alex , Blackstone Eugene H , Rothberg Michael B
Published: September 2021

Objectives

To describe variation in and drivers of contemporary preoperative cardiac stress testing.

Setting

A dedicated preoperative risk assessment and optimisation clinic at a large integrated medical centre from 2008 through 2018.

Participants

A cohort of 118 552 adult patients seen by 104 physicians across 159 795 visits to a preoperative risk assessment and optimisation clinic.

Main outcome

Referral for stress testing before major surgery, including nuclear, echocardiographic or electrocardiographic-only stress testing, within 30 days after a clinic visit.

Results

A total of 8303 visits (5.2%) resulted in referral for preoperative stress testing. Key patient factors associated with preoperative stress testing included predicted surgical risk, patient functional status, a previous diagnosis of ischaemic heart disease, tobacco use and body mass index. Patients living in either the most-deprived or least-deprived census block groups were more likely to be tested. Patients were tested more frequently before aortic, peripheral vascular or urologic interventions than before other surgical subcategories. Even after fully adjusting for patient and surgical factors, provider effects remained important: marginal testing rates differed by a factor-of-three in relative terms and around 2.5% in absolute terms between the 5th and 95th percentile physicians. Stress testing frequency decreased over the time period; controlling for patient and physician predictors, a visit in 2008 would have resulted in stress testing approximately 3.5% of the time, while a visit in 2018 would have resulted in stress testing approximately 1.3% of the time.

Conclusions

In this large cohort of patients seen for preoperative risk assessment at a single health system, decisions to refer patients for preoperative stress testing are influenced by various factors other than estimated perioperative risk and functional status, the key considerations in current guidelines. The frequency of preoperative stress testing has decreased over time, but remains highly provider-dependent.
Tingbjerg Changing Diabetes: a protocol for a long-term Supersetting initiative to promote health and prevent type 2 diabetes among people living in an ethnically and socioeconomically diverse neighbourhood in Copenhagen, Denmark
Authors: Tørslev Mette Kirstine , Andersen Pernille Tanggaard , Nielsen Asser Vittrup , Petri Marie , Termansen Tina , Vardinghus-Nielsen Henrik , Varming Annemarie , Bloch Paul
Published: September 2021

Introduction

Type 2 diabetes is an escalating public health problem closely related to socioeconomic position. There is increased risk of type 2 diabetes in disadvantaged neighbourhoods where education, occupation and income levels are low. Meanwhile, studies show positive health outcomes of participatory community interventions pointing towards the need for increased health promotion and prevention of type 2 diabetes in local communities. This study protocol describes Tingbjerg Changing Diabetes (TCD), a community-based health promotion and type 2 diabetes prevention initiative in Tingbjerg, a disadvantaged neighbourhood in Copenhagen, Denmark.

Methods and analysis

TCD is a long-term, complex intervention, implemented in three phases from 2014 to 2032, focusing on partnership formation (phase 1, 2014–2019), developing and implementing action for health (phase 2, 2019–2030) and diffusion of knowledge (phase 3, 2022–2032). The Supersetting principles act as guidelines for development and implementation of all intervention activities of TCD, involving several population groups in a variety of everyday life settings. The implementation of TCD draws on Community Action Research design and methodologies. TCD’s evaluation and research strategy is interdisciplinary, pragmatic and multimethod, unfolding at three levels of operation: (A) evaluating activities, (B) researching cross-cutting topics, and (C) researching methods and approaches.

Ethics and dissemination

TCD has been approved by the Danish Data Protection Agency. Accordingly, the initiative is carried out in adherence to rules and regulations of the Danish Data Protection Agency. As data contain no personal identifiable or sensitive data, no clearance from the Danish National Ethical Review Board can be obtained according to Danish regulations. Citizen, local agents and stakeholders are engaged in the design and execution of TCD to ensure usefulness, reflexive interpretation of data, relevance and iterative progression of interventions. Results will be published in international peer-reviewed scientific journals, presented at conferences and through public media including TCD home page, podcasts and videos.
What are determinants of utilisation of pharmaceutical anticancer treatment during the last year of life in Norway? A retrospective registry study
Authors: Bugge Christoffer , Kaasa Stein , Sæther Erik Magnus , Melberg Hans Olav , Sonbo Kristiansen Ivar
Published: September 2021

Objectives

The objective of this study was to investigate the use of, and predictors for, pharmaceutical anticancer treatment (PACT) towards the end of a patient’s life in a country with a public healthcare system.

Design

Retrospective registry study.

Setting

Secondary care in Norway.

Participants

All Norwegian patients with cancer (International Classification of Diseases tenth revision (ICD-10) codes C00–99, D00–09, D37–48) in contact with a somatic hospital in Norway between 2009 and 2017 (N=420 655). Analyses were performed on a subsample of decedents with follow-back time of more than 1 year (2013–2017, N=52 496).

Interventions

N/A.

Primary and secondary outcome measures

Proportion of patients receiving PACT during the last year and month of life. We calculated CIs with block bootstrapping, while predictors of PACT were estimated with logistic regression.

Results

24.0% (95% CI 23.4% to 24.6%) of the patients received PACT during the last year of life and 3.2% (95% CI 3.0% to 3.5%) during their final month. The proportion during the last month was highest for multiple myeloma (12.7%) and breast cancer (6.5%) and lowest for urinary tract (1.1%) and prostate and kidney cancer (1.4%). Patients living in northern (OR 0.80, 95% CI 0.68 to 0.94) and western (OR 0.85, 95% CI 0.75 to 0.96) Norway had lower odds of PACT during the last month, while patients with myeloma (OR 3.0, 95% CI 2.5 to 3.7) and breast (OR 1.4, 95% CI 1.1 to 1.6) had higher odds. Kidney cancer (OR 0.25, 95% CI 0.2. to 0.4), urinary tract (OR 0.38, 95% CI 0.3 to 0.5) and prostate cancer (OR 0.4, 95% CI 0.3 to 0.5) were associated with lower probability of receiving PACT within the last month.

Conclusions

The proportion of patients receiving PACT in Norway is lower than in several other industrialised countries. Age, type of cancer and area of living are significant determinants of variation in PACT.
Exploration of a quality improvement process to standardised preoperative tests for a surgical procedure to reduce waste
Authors: Shahid Rabia , Chaya Malone , Lutz Ian , Taylor Brian , Xiao Lily , Groot Gary
Published: September 2021

Background

Preoperative tests are done to determine a patient’s fitness for anaesthesia and surgery.

Local problem

Although routine tests before surgery in the absence of specific clinical indications are not recommended, we observed high volumes of routine preoperative tests were performed in our institution. We describe a process to implement a standardised preoperative investigational approach to reduce unnecessary testing before surgeries.

Methods

A series of six Plan-Do-Study-Act (PDSA) cycles was conducted for root cause analysis and process mapping, development of standardised tool (GRID), collection of baseline data, education and feedback, pilot testing and implementation and uptake of GRID.

Root cause analysis revealed a lack of awareness of guidelines and a lack of a standardised tool to guide preoperative testing. We undertook a pilot quality improvement project to reduce unnecessary testing before knee and hip arthroplasty by developing and implementing a standardised tool (GRID) and engaging all stakeholders.

Interventions

A clinical development team (CDT) was formed, including all the stakeholders. Our CDT focused on a continuous rapid cycle improvement strategy.

Results

After implementation of the tool in a subgroup of patients undergoing elective hip or knee arthroplasty, unnecessary coagulation tests (activated partial thromboplastin time and the international normalised ratio), electrolyte/renal panel tests and electrocardiograms were reduced by 81% (91%–17%), 81% (41%–7%) and 68% (35%–11%), respectively. No surgery was delayed or cancelled due to tests not performed before surgery.

Conclusions

A standardised preoperative investigational approach based on patients’ medical conditions rather than routine testing can reduce unnecessary tests before surgery. Further, implementing guidelines is more complex than developing guidelines. Hence, continuous PDSA cycles are essential to evaluate the processes in a quality improvement project. It can take time to build teams and have shared goals; however, once this is achieved, the success of a quality improvement project is certain.
The relative reinforcing value of snack food is a significant predictor of fat loss in women with overweight or obesity
Authors: Hintze Luzia Jaeger , Doucet Éric , Goldfield Gary S.
Published: September 2021

Reinforcing Relative Value (RRV) of food and impulsivity are associated with energy intake and obesity. This study investigated the degree to which changes in RRV and impulsivity independently or interactively predict changes in body weight and composition in women with overweight or obesity engaged in either fast or slow weight loss programs. Body weight, body composition, impulsivity (Barratt Impulsiveness Scale), and RRV snack (computerized Behavioural Choice Task) were measured at baseline and post-intervention in 30 women with obesity undergoing either slow (n = 14, –500 kcal/day, 20 weeks) or fast (n = 16, –1000 kcal/day, 10 weeks) weight reduction. No group × time effects were noted on body composition, impulsivity, or RRV, so participants from both groups were pooled for analysis. Multiple regression analyses indicated that none of the impulsivity variables predicted weight or fat mass (FM) loss. However, ΔRRV snack predicted ΔFM (r = 0.40, p = 0.046), whereby greater increases in RRV snack were associated with less FM loss. The results indicate that different rates of weight loss do not differentially affect RRV snack or impulsivity traits. However, changes in RRV snack predicted FM loss, suggesting that dietary interventions that either mitigate increases or foster reductions in the RRV snack may yield greater reductions in adiposity. Trial Registration clinicaltrials.gov identifier: NCT04866875.

Novelty: No differences in RRV of food were noted between fast and slow weight loss. Weight loss from combined fast and slow groups led to a moderate-sized reduction in total impulsivity. Greater diet-induced increases in RRV snacks were associated with less body fat loss.