bluuebunny/crossref_metadata_2025 huggingface dataset:
Russia
Authors: Porter Robert
Published: November 2023

Contemporary Russian writing—writing in Russian, that is: I cannot be concerned here with writing done in the former Soviet Union in its various other languages—presents special problems of definition. Is one to deal with works being written and—promptly—published now? Or to include those finally being published in Russia, although they were written many years before when, for ideological reasons, they had no hope of publication? And what part does literature written and/or published hitherto only in emigration play in what is today a literary world governed primarily by the market-place? The situation that seems to have emerged in the post-Communist era is one in which serious works exist in an uneasy and, as some Russian intellectuals see it, destructive symbiosis with popular fiction, outright trash, and pornography.
Scandinavia
Authors: Garton Janet
Published: November 2023

For many years after 1945, Scandinavian writers were preoccupied with the subject of the Second World War and its repercussions: with the Finnish winter war against Russia, the German occupation of Norway and Denmark, and the compromised neutrality of Sweden. The late 1940s and 1950s were dominated by war literature, and some major contributions even came in the 1960s, such as the Danish Communist Hans Scherfig’s (1905-79) attack on his country’s betrayal of its Communists in Frydenholm (1962), or the investigation of Sweden’s treatment of Baltic refugees in The Legionnaires (1968), by Per Olov Enquist (b. 1934). Yet, broadly speaking, by the early 1960s writers were more concerned with formal experimentation. As the decade advanced, however, other political concerns came to the fore.
Scotland
Authors: Boddy Kasia
Published: November 2023

As the work of novelists such as Alasdair Gray (b. 1934), James Kelman (b. 1946), and A. L. Kennedy (b. 1965) finds ever-increasing acclaim, many are heralding another renaissance in Scottish writing; the first being that associated with such writers as Hugh MacDiarmid, Edwin Muir, and Lewis Grassie Gibbon in the 1920s and 1930s. While those writers largely drew on a threatened rural way of Hfe which they felt contained the essence of Scottish identity, the writers whose work is acclaimed today tend to explore an urban Scotland.
Spain
Authors: Six Abigail Lee
Published: November 2023

In 1960 Spain was just beginning to emerge from the most isolated, oppressive, and economically lean years of General Franco’s dictatorship. As the decade wore on, Spanish society gradually grew more open: tourism started to transform the country, bringing not only much-needed money but also the shock of a new contact with foreigners. The availability of books by Spanish writers in exile and non-Spanish writers considered subversive by the regime improved, too. In 1966 an important new law was passed: except in the theatre, there was no longer any need to submit work to the censors before publication. Censorship would only be post facto. This apparent improvement, however, masked a more insidious form of censorship that, according to one writer of the period, Juan Goytisolo, was already troubling him at the beginning of the decade: more than ever, writers were now going to have to be their own censors.
Spanish America
Authors: Wood Michael
Published: November 2023

Spanish American culture did not become sophisticated in the 1960s; it had been sophisticated for a long time before that. But it agreed to take its sophistication for granted, to let it loose as it were: it created an extensive literature which saw this sophistication as both precious and ordinary, to be deployed and enjoyed, not denied or exaggerated or apologized for.
Screening for depression in the Serbian general population sample: an alternative to the traditional patient health questionnaire-9 cut-off score
Authors: Mihić Ljiljana , Knežević Goran , Lazarević Ljiljana B , Marić Nadja P
Published: November 2023

Background

The Patient Health Questionnaire (PHQ-9) score ≥ 10 balances best sensitivity and specificity when detecting probable depression in patients. In the general population, different cut-offs are suggested. European studies on general populations validating the PHQ-9 against a diagnostic interview to detect depression are rare.

Methods

This was a cross-sectional observational epidemiological survey using multistage household probabilistic sampling to recruit a representative adult sample (N = 1203; age = 43.7 ± 13.6; 48.7% male). Mental disorders including current major depressive episode (MDE) were observer-rated (Mini International Neuropsychiatric Interview). The PHQ-9, quality of life (QoL), and loneliness were self-assessed. We performed validity and reliability tests of the PHQ-9 and receiver operating curve (ROC) analysis.

Results

The Serbian PHQ-9 was internally consistent and correlated in the expected directions with QoL and loneliness. At the cut-off score ≥ 8, sensitivity was .85 and specificity was .91. ROC analysis showed that the area under the curve was .95, indicating that the Serbian PHQ-9 can discriminate very well between persons with/without MDE.

Conclusions

When the PHQ-9 is assessed against the structured diagnostic interview in the general population to detect depression, the cut-off of ≥8 balances best sensitivity and specificity.
Disparities in adverse impacts of the COVID-19 pandemic by disability status in metropolitan Texas
Authors: Chakraborty J , Grineski S E , Collins T W , Aun J J
Published: November 2023

Background

This article addresses the urgent need for more evidence-based research using primary data to document how the COVID-19 pandemic affected the health and social wellbeing of disabled individuals. Our study sought to determine if adults with disabilities, and with specific types of disability, were more likely to suffer adverse health and social impacts related to COVID-19 than nondisabled adults in metropolitan Texas, during the first 18 months of the pandemic.

Methods

We collected primary data from randomly selected residents in eight Texas metropolitan areas through a bilingual telephone survey in July 2021. Statistical analysis comprised multivariable generalized estimating equations that control for relevant sociodemographic and COVID-related risk factors, and spatial clustering.

Results

Disabled survey respondents had been more adversely affected by COVID-19 than nondisabled respondents, in terms of mental and physical health, health care access, living conditions and social life. Significant disparities were also found for almost all COVID-19 impacts when the disabled category was disaggregated by disability type. Respondents experiencing cognitive and independent living difficulties were negatively impacted in all five areas of life examined.

Conclusions

Findings emphasize the need to consider a wide range of impacts associated with the COVID-19 pandemic that negatively affect the health and social wellbeing of disabled persons, as well as develop disability-inclusive policies that provide adequate protections.
Biological/targeted synthetic DMARDs do not arrest bone loss in patients with rheumatoid arthritis: a multicenter prospective observational study
Authors: Sonomoto Koshiro , Nakayamada Shingo , Fujino Yoshihisa , Miyata Hiroko , Kubo Satoshi , Fujita Yuya , Inoue Yoshino , Matsunaga Satsuki , Iwata Shigeru , Hanami Kentaro , Todoroki Yasuyuki , Yoshinari-Korekoda Hiroko , Kawabe Akio , Yamaguchi Ayako , Ueno Masanobu , Satoh-Kanda Yurie , Kanda Ryuichiro , Funada Masashi , Ohkubo Naoaki , Kusaka Katsuhide , Kosaka Shumpei , Nagayasu Atsushi , Fukuyo Shunsuke , Nawata Masao , Miyazaki Yusuke , Tokunaga Mikiko , Tanaka Kenichi , Okada Yosuke , Tanaka Yoshiya
Published: November 2023

Objective

To elucidate the differential effects of biological/target synthesized DMARDs (b/tsDMARDs) on bone metabolism in patients with rheumatoid arthritis (RA) in a real-world cohort.

Methods

This was a multicentre prospective observational study of RA patients enrolled at the time of first b/tsDMARDs administration. Bone mineral density (BMD) and bone turnover markers (BTMs) were measured during the 52-week observation. The study was designed to enrol all eligible RA patients. The end-points were differences in changes in BMD according to b/tsDMARD type, and the correlation between BMD and BTMs.

Results

A total of 1164 patients were enrolled in this study. b/tsDMARDs improved RA disease activity from mean CDAI 25.5 at baseline to 4.5 at week 26. Patients not receiving anti-osteoporotic agents (anti-OP) at baseline with no history of fracture experienced a significant decrease in both femoral neck (F: mean 0.666–0.655 g/cm3) and radial (R: 0.518–0.514) BMD at week 26. Despite maintaining low CDAI levels during weeks 26–52 (5.3–4.4), there was a continued decline in BMD (F: 0.653, R: 0.509. Weeks 52). None of the b/tsDMARDs type preserved BMD. Conversely, patients receiving anti-OP at baseline maintained stable BMD throughout the study (Weeks 0/26/52. F: 0.551/0.551/0.555, R: 0.415/0.416/0.415). Although BTMs were changed by b/tsDMARDs, the changes were unrelated to those in BMD.

Conclusion

Our study suggested the progression of osteoporosis in RA patients during b/tsDMARDs treatment without anti-OP. BTMs may not reflect BMD change. Regular monitoring of BMD in RA should be considered for early management of osteoporosis.
Predictors and prognosis of tracheostomy in relapsing polychondritis
Authors: Yin Ruxue , Xu Dong , Wang Qian , Li Mengtao , Zhang Wen , Zhang Fengchun , Zeng Xiaofeng , Jiang Nan , Hou Yong
Published: November 2023

Objective

Airway obstruction can occur in patients with relapsing polychondritis with laryngeal involvement, occasionally requiring tracheostomy to avoid serious complications. Herein, we assessed the risk factors for tracheostomy and developed a risk prediction model.

Methods

Clinical characteristics of patients with relapsing polychondritis, with and without tracheostomy, were compared using multivariate logistic regression analysis to identify risk factors. A nomogram was developed to predict the population at risk of requiring tracheostomy.

Results

In total, 232 patients with relapsing polychondritis were reviewed, of whom 146 had laryngeal involvement. Among them, 21 underwent a tracheostomy. Multivariate logistic analysis identified ages ≤25 or ≥65 years [P < 0.001, odds ratio (OR) 24.584, 95% CI 5.310–113.815], laryngotracheal oedema (P < 0.001, OR 26.685, 95% CI 4.208–169.228) and pulmonary infection (P = 0.001, OR 18.834, 95% CI 3.172–111.936) as independent risk factors for tracheostomy. A nomogram with a C-index of 0.936 (95% CI 0.894–0.977) was established based on the multivariate analysis. Internal bootstrap resampling (1000 repetitions) confirmed sufficient discriminatory power with a C-index of 0.926. Decision curve analysis indicated a superior net benefit of the nomogram. Tracheostomy was associated with a significant increase in the in-hospital mortality rate (P = 0.021), but it did not affect the long-term survival rate (P = 0.706).

Conclusion

Tracheostomy is associated with an increase in the short-term mortality rate but does not affect the long-term survival rate. The nomogram developed in this study may help identify patients at high risk for tracheostomy and aid in clinical decision-making.
Detection limit variation against coarse aerosol during airborne contamination measurement with continuous air monitor
Authors: Dougniaux Grégoire , Hoarau Gwenaël
Published: November 2023

In nuclear facilities, the mandatory airborne contamination surveillance is operated by continuous air monitors (CAMs). It samples the ambient air on a filter and measures the deposited activity. It is designed to trig an alarm whenever the measured activity concentration exceeds a defined threshold. However, in some sites, such as dismantling nuclear sites, a high rate of false alarm is experienced, mainly for artificial alpha. It has been shown that false alarms are directly related to a sudden variation of the aerosol mass sizes distribution, i.e. a wrong detection limit (DL) evaluation. Experiments on the ICARE tests bench have been carried out to compare the CAM’s DL and an estimated DL as a function of the aerosol characteristics, to the measured one. This new estimation shows significant improvements over the previous one and highlights the need to consider aerosol characteristics for a correct airborne contamination measurement.
Study of the effect of temperature and water content on radon exhalation from phosphate using LR-115 detectors
Authors: Jabbade Meryame , Nachab Abdellatif , Elouardi Elmokhtar , Nourreddine Abdel-Mjid , Errami Ezzoura , Benjelloun Mohammed , Fahad Mohammed
Published: November 2023

A study of the influence of moisture content on the radon exhalation rate from phosphate samples (with and without consideration of the back diffusion effect) was performed using the sealed cup technique. The mass exhalation rate was found to increase with an increase in moisture content, reaching a maximum value of 2.414 ± 0.034 Bq kg−1 h−1 with a moisture content of 10%. However, the mass exhalation rate decreased with a continued increase in moisture content above 25%. The mass exhalation rate was also measured at different temperatures between −10 and 50°C. The obtained results show that the mass exhalation rate increases linearly with temperature. We point out that all the obtained values of radon exhalation rate are lower than the world average radon exhalation rate (57.6 Bq m−2 h−1).
Norm in cultivated honey in Malaysia and concomitant effective dose to consumers
Authors: Khandaker Mayeen U , Zayadi Nurul S B , Sani Siti Fairus A , Bradley David A , Osman Hamid , Alzamil Yasser , Almeshari Meshari , Sayyed M I , Sulieman Abdelmoneim
Published: November 2023

Present study concerns the radiological character of Malaysian honey. A total of 18 samples (representative of the various most common types) were obtained from various honey bee farms throughout the country. Using a high-purity germanium γ-ray spectroscopic system, the samples were analysed for the naturally occurring radionuclides 226Ra, 228Ra and 40K. The respective range of activities (in Bq/kg) was: 3.49 ± 0.35 to 4.51 ± 0.39, 0.99 ± 0.37 to 1.74 ± 0.39 and 41.37 ± 3.26 to 105.02 ± 6.91. The estimated associated committed effective doses were derived from prevailing data on national consumption of honey, the annual dose being found low compared with the UNSCEAR reference dose limit of 290 μSv y−1. The estimated threshold consumption rate for honey indicates a maximum intake of 339 g/d, which poses an insignificant radiological risk to public health; however, the total dietary exposure may not, the guidance level of 290 μSv y−1 being applicable to dietary intake of all foodstuffs. The study is in support of the cultivation of a healthy lifestyle, acknowledging prevailing radioactivity within the environment.
The presence of toxic heavy metals in tuna fishes from Laccadive sea and concomitant health risk
Authors: Nadhiya Aishath , Khandaker Mayeen U , Mahmud Sultan , Abdullah Wan H
Published: November 2023

Concentrations of heavy metals in Yellowfin and Skipjack tuna fishes from the Laccadive sea were determined by inductively coupled plasma optical emission spectroscopy (ICP-OES) to evaluate the human health hazards via their consumption. The samples were collected from different atolls of Maldives to ensure a good representation of sample distribution. The metal concentration in tuna fish is found to be below the maximum tolerable limit set by different international organisations. The target hazard quotient values for individual metals were well below the limiting value of 1, indicating an insignificant health risk via the dietary intake of fish. The maximum targeted cancer risk value was 10 −4, indicating low carcinogenic risk from the consumption of tuna fish from the Maldives. Hence, the consumption of tuna from the Laccadive Sea is safe for human health.
Distribution of naturally occurring radionuclides and gamma dose rate assessment in the soils of high background natural radiation area Odisha, India
Authors: Veerasamy Nimelan , Sahoo Sarata K , Natarajan Thennaarassan , Inoue Kazumasa , Fukushi Masahiro , Ramola Rakesh C
Published: November 2023

A study on the activity concentration of primordial radionuclides 226Ra, 232Th and 40K was carried out on the surface soil samples collected from the coastal villages between Chhatrapur and Gopalpur regions of high background natural radiation area Odisha, India, using high purity germanium gamma spectroscopy. The mean activity concentrations of 226Ra, 232Th and 40K were found to be 231, 1692 and 250 Bq/kg, respectively. The total mean absorbed dose owing to the presence of 226Ra, 232Th and 40K was 1139 nGy/h. The mean annual effective dose was found to be 1397 μSv/y and higher than the UNSCEAR average value 70 μSv/y.
UCHL1 maintains microenvironmental homeostasis in goat germline stem cells
Authors: Yang Donghui , Zhang Mengfei , Chen Wenbo , Lu Qizhong , Wan Shicheng , Du Xiaomin , Li Yunxiang , Li Balun , Wu Wenping , Wang Congliang , Li Na , Peng Sha , Tang Haiyang , Hua Jinlian
Published: November 2023

Spermatogonial stem cells (SSCs) play a crucial role in mammalian spermatogenesis and maintain the stable inheritance of the germline in livestock. However, stress and bacterial or viral infections can disrupt immune homeostasis of the testes, thereby leading to spermatogenesis destruction and infertility, which severely affects the health and productivity of mammals. This study aimed to explore the effect of ubiquitin C‐terminal hydrolase L1 (UCHL1) knockdown (KD) in goat SSCs and mouse testes and investigate the potential anti‐inflammatory function of UCHL1 in a poly(I:C)‐induced inflammation model to maintain microenvironmental homeostasis. In vitro, the downregulation of UCHL1 (UCHL1 KD) in goat SSCs increased the expression levels of apoptosis and inflammatory factors and inhibited the self‐renewal and proliferation of SSCs. In vivo, the structure of seminiferous tubules and spermatogenic cells was disrupted after UCHL1 KD, and the expression levels of apoptosis‐ and inflammation‐related proteins were significantly upregulated. Furthermore, UCHL1 inhibited the TLR3/TBK1/IRF3 pathway to resist poly(I:C)‐induced inflammation in SSCs by antagonizing HSPA8 and thus maintaining SSC autoimmune homeostasis. Most importantly, the results of this study showed that UCHL1 maintained immune homeostasis of SSCs and spermatogenesis. UCHL1 KD not only inhibited the self‐renewal and proliferation of goat SSCs and spermatogenesis but was also involved in the inflammatory response of goat SSCs. Additionally, UCHL1 has an antiviral function in SSCs by antagonizing HSPA8, which provides an important basis for exploring the specific mechanisms of UCHL1 in goat spermatogenesis.
Surgical Implications of Soft Tissue Depth in Primary Total Hip Arthroplasty
Authors: Oldham Blaine , Rinehart Dustin , Youngman Tyler , Huo Michael
Published: November 2023

Background:

Morbid obesity has been identified as a risk factor for complications in total hip arthroplasty (THA). However, the impact of the adipose tissue distribution near the surgical site has not been adequately studied. We aimed to characterize the complication rates associated with varying soft tissue depth around the operative hip as measured on plain films.

Methods:

We performed a retrospective review of primary THAs at our institution from 2009 to 2020. A total of 106 patients met inclusion criteria. Propensity score matching was used to match the patients that required reoperation (n=13) to a cohort of those that did not (n=33) based upon demographics, BMI, and age. Four standardized measurements were taken, and statistical analyses were performed to determine if complication differences existed between cohorts.

Results:

There was no statistical difference between the non-reoperation cohort or the reoperation cohort in age (65.0 vs. 65.4, P=0.462) or BMI (39.4 vs. 40.9, P=0.108). There was no significant difference between the two cohorts for all four measurements (P=0.296, P=0.369, P=0.463, P=0.321). A subgroup analysis of patients with BMI ≥40 (n=23) demonstrated that individuals in the reoperation cohort had a higher value of measurements 3 and 4 (237.2 vs. 274.6, P=0.041; 236.5 vs. 284.1, P=0.015).

Conclusions:

A standardized measurement of thigh width on an AP pelvis plain film may help surgeons identify a subset of patients (BMI ≥40) at elevated risk for complication in primary THA.
Microsurgery in the Sickle Cell Trait Population: Can it Be Safely and Successfully Performed?
Authors: Eliseo Sara , Berlin Levana , Mansour Ahmed M. , Hansen Susan , Ranganath Bharat , Wallace Sean J.
Published: November 2023

Free-tissue transfer reconstruction in patients with sickle cell anemia risks failure due to polymerization of sickle hemoglobin within the flap microcirculation. However, outcomes vary, as the amount of polymerization is dependent on factors such as disease phenotype/diagnosis, degree of hypoxia, and intracellular dehydration. Most of the literature focuses on patients with sickle cell disease, which produces higher concentrations of sickle hemoglobin and, therefore, is a contraindication to microvascular reconstruction. Fewer reports describe microsurgery in patients with sickle cell trait (SCT) who carry the heterozygous phenotype. Here, we present a case in which a patient with SCT underwent microsurgical breast reconstruction with deep inferior epigastric perforator free-tissue transfer. The 52-year-old woman had previously experienced a failed alloplastic-based reconstruction after radiation therapy for breast cancer. In our case, clinical and Doppler examinations demonstrated that arterial and venous anastomoses had remained patent; so the patient was discharged on postoperative day 4. Blistering developed on postoperative day 8, and by day 15 there was partial necrosis of the inferior-lateral aspect of the deep inferior epigastric perforator flap. Debridement and closure resolved the issue, and at 5 months postprocedure, the flap remained well-perfused and well-incorporated. This case, presented here with patient consent, reports a successful outcome of microsurgical reconstruction in a patient with SCT. It expands the limited evidence to support the safety and feasibility of autologous surgical interventions for patients with the heterozygous phenotype of sickle cell anemia.
Low-density lipoprotein cholesterol, non-high-density lipoprotein cholesterol and apolipoprotein B for cardiovascular care
Authors: Bilgic Selin , Sniderman Allan D.
Published: November 2023

Purpose of review

Some experts and consensus groups continue to argue that apolipoprotein B (apoB) should not be introduced broadly into clinical care. But, too often, the present approach to clinical care is not succeeding. An important reason for this failure, we believe, is that the conventional approach limits what the expert clinician can accomplish and is too complex, confusing, and contradictory for primary care physicians to apply effectively in their practise.

Recent findings

There are four major reasons that apoB should be measured routinely in clinical care. First, apoB is a more accurate marker of cardiovascular risk than LDL-C or non-HDL-C. Second, the measurement of apoB is standardized whereas the measurements of LDL-C and non-HDL-C are not. Third, with apoB and a conventional lipid panel, all the lipid phenotypes can be simply and accurately distinguished. This will improve the care of the expert. Fourth, apoB, as the single measure to evaluate the success of therapy, would simplify the process of care for primary care physicians.

By introducing apoB broadly into clinical care, the process of care will be improved for both the expert and the primary care physician, and this will improve the outcomes of care.
The Impact of Resilience and Perceived Autonomy Support on Medication Adherence Among Rural Older Adults With Hypertension
Authors: Besel Jamie M. , Insel Kathleen C. , Williams Geoffrey C.
Published: November 2023

Background

Adherence to antihypertension medications has been explored in previous studies; however, these studies generally focus on individuals who reside in urban areas. Improved understanding is needed regarding rural older adults who are self-managing medications for hypertension and the motivational factors that may influence adherence.

Objectives

The purpose of this study was to examine medication adherence among rural older adults with hypertension and the association with motivational factors as defined in self-determination theory, including quality of motivation (autonomous vs controlled), perceived competence, perceived autonomy support, and basic psychological needs satisfaction. Rural nursing theory was also used to explore the concept of resilience.

Methods

This cross-sectional study involved 80 older adults (≥65 years old) self-managing at least 1 prescribed medication for managing their hypertension. Participants ranged in age from 65 to 89 (mean [SD], 74.04 [6.18]) years from rural areas in the northwest. Participants completed a demographic questionnaire, a measure of medication adherence, and questionnaires to assess perceived autonomy support, basic needs satisfaction, autonomous and controlled motivation, perceived competence, and resilience.

Results

Correlational analysis and multiple regression were used to examine associations and predict adherence. Perceived autonomy support, resilience, cost of medication, and medication regimen complexity were the only variables significantly associated with medication adherence and predicted adherence. Resilience mediated the relationship between perceived autonomy support and medication adherence.

Conclusions

Overall, findings indicate high levels of adherence. Interventions that enhance perceptions of autonomy support and resilience may be useful in managing hypertension.
Pediatric interventional bronchoscopy: from early limitations to achievable opportunities
Authors: Januska Megan N. , Kaspy Kimberley , Bozkanat Kubra M. , Vicencio Alfin G.
Published: November 2023

Purpose of review

The rapid evolution of bronchoscopy equipment and technologies, from the introduction of the 1.1 mm flexible cryoprobe to the use of navigational and robotic bronchoscopy, has afforded unprecedented opportunities for pediatric advanced diagnostic and interventional bronchoscopy. While there is growing interest among pediatric pulmonologists to incorporate these new techniques into their practice, the current pediatric landscape is characterized by few practicing interventional bronchoscopists, scant published literature, and no formal training programs.

Recent findings

While the majority of the published literature consists of case reports and small case series, the increased application of new techniques is starting to yield larger and more structured studies that will be able to provide more objective commentary on the proposed indications, safety, and efficacy of such techniques in the pediatric population.

For many decades, progress in pediatric advanced diagnostic and interventional bronchoscopy was slow and deliberate, limited by the lack of appropriately sized equipment and experienced interventional bronchoscopists. The current opportunities afforded require equal, or perhaps even more, vigilance as pediatric pulmonologists employ new equipment and technologies and define new practices and standards of care. Importantly, this review is meant to serve as a general conspectus of pediatric advanced diagnostic and interventional bronchoscopy and not a consensus guideline for the performance of advanced or even routine bronchoscopy in the pediatric population. For technical standards of pediatric bronchoscopy, refer to existing guidelines [1,2].
The effect of psychological factors on pain outcomes: lessons learned for the next generation of research
Authors: Crombez Geert , Veirman Elke , Van Ryckeghem Dimitri , Scott Whitney , De Paepe Annick
Published: November 2023

Big data and machine learning techniques offer opportunities to investigate the effects of psychological factors on pain outcomes. Nevertheless, these advances can only deliver when the quality of the data is high and the underpinning causal assumptions are considered. We argue that there is room for improvement and identify some challenges in the evidence base concerning the effect of psychological factors on the development and maintenance of chronic pain. As a starting point, 3 basic tenets of causality are taken: (1) cause and effect differ from each other, (2) the cause precedes the effect within reasonable time, and (3) alternative explanations are ruled out. Building on these tenets, potential problems and some lessons learned are provided that the next generation of research should take into account. In particular, there is a need to be more explicit and transparent about causal assumptions in research. This will lead to better research designs, more appropriate statistical analyses, and constructive discussions and productive tensions that improve our science.
Dental Rehabilitation of the Unilateral Cleft Dental Gap: A Single Institution Experience With Long-Term Follow-Up
Authors: Lee Kevin C. , Yau Vicky , Khoshnevisan Mohammad A. , Eisig Sidney B.
Published: November 2023

Objective:

The purpose of this study was to identify factors associated with the management of the cleft dental gap after alveolar bone grafting.

Methods:

This was a retrospective cohort study of patients with unilateral cleft lip and alveolus or palate who had successful alveolar bone grafting. Our primary study outcome was alveolar cleft management (orthodontic closure or space maintenance). Our secondary study outcome was the rate of fixed dental rehabilitation. Univariate comparisons were made with SAS 9.4.

Results:

The final study sample consisted of 54 patients. Most patients were treated with orthodontic closure (55.6%). Patients missing multiple teeth (P < 0.01) were less likely to receive orthodontic closure. Orthodontic closure was not associated with differences in intermaxillary midline coincidence (P = 0.22) or the need for LeFort advancement (P = 0.15). Only 41.7% of patients who were managed with space maintenance obtained a fixed prosthesis. Hispanic ethnicity (P < 0.01) and Medicaid insurance (P < 0.01) were associated with lower rates of fixed dental rehabilitation.

Conclusions:

Orthodontic closure was the most common approach, and it did not result in significant maxillary midline distortion. Less than half of patients treated with space maintenance obtained fixed restorations. Socioeconomic barriers are likely preventing access to definitive dental rehabilitation in patients with unilateral cleft lip and alveolus or palate.
Eliminating the benzos: A benzodiazepine-sparing approach to preventing and treating alcohol withdrawal syndrome
Authors: McCullough Mary Alyce , Miller Preston R. , Martin Tamriage , Rebo Kristin A. , Stettler Gregory R. , Martin Robert Shayn , Cantley Morgan , Shilling Elizabeth H. , Hoth James J. , Nunn Andrew M.
Published: November 2023

BACKGROUND

Alcohol withdrawal syndrome (AWS) represents significant cost to the hospitalized trauma population from a clinical and financial perspective. Historically, AWS has been managed with benzodiazepines. Despite their efficacy, benzodiazepines carry a heavy adverse effect profile. Recently, benzodiazepine-sparing protocols for the prophylaxis and treatment of AWS have been used in medical patient populations. Most existing benzodiazepine-sparing protocols use phenobarbital, while ours primarily uses gabapentin and clonidine, and no such protocol has been developed and examined for safety and efficacy specifically within a trauma population.

METHODS

In December of 2019, we implemented our benzodiazepine-sparing protocol for trauma patients identified at risk for alcohol withdrawal on admission. Trauma patients at risk for AWS admitted to an academic Level 1 trauma center before (conventional) and after (benzodiazepine-sparing [BS]) protocol implementation were compared. Outcomes examined include morphine milligram equivalent dosing rates and lorazepam equivalent dosing rates as well as the Clinical Institute Withdrawal Assessment for Alcohol, revised (CIWA-Ar) scores, hospital length of stay, intensive care unit length of stay, and ventilator days.

RESULTS

A total of 387 conventional and 134 benzodiazepine sparing patients were compared. Injury Severity Score (13 vs. 16, p = 0.10) and admission alcohol levels (99 vs. 149, p = 0.06) were similar. Patients in the BS pathway had a lower maximum daily CIWA-Ar (2.7 vs. 1.5, p = 0.04). While mean morphine milligram equivalent per day was not different between groups (31.5 vs. 33.6, p = 0.49), mean lorazepam equivalents per day was significantly lower in the BS group (1.1 vs. 0.2, p < 0.01). Length of stay and vent days were not different between the groups.

CONCLUSION

Implementation of a benzodiazepine-sparing pathway that uses primarily clonidine and gabapentin to prevent and treat alcohol withdrawal syndrome in trauma patients is safe, reduces the daily maximum CIWA-Ar, and significantly decreases the need for benzodiazepines. Future studies will focus on outcomes affected by avoiding AWS and benzodiazepines in the trauma population.

LEVEL OF EVIDENCE

Therapeutic/Care Management; Level IV.
Integrated longitudinal multi-omics study identifies immune programs associated with COVID-19 severity and mortality in 1152 hospitalized participants
Authors: Gygi Jeremy P. , Maguire Cole , Patel Ravi K. , Shinde Pramod , Konstorum Anna , Shannon Casey P. , Xu Leqi , Hoch Annmarie , Jayavelu Naresh Doni , Network IMPACC , Haddad Elias K. , Reed Elaine F. , Kraft Monica , McComsey Grace A. , Metcalf Jordan , Ozonoff Al , Esserman Denise , Cairns Charles B. , Rouphael Nadine , Bosinger Steven E. , Kim-Schulze Seunghee , Krammer Florian , Rosen Lindsey B. , van Bakel Harm , Wilson Michael , Eckalbar Walter , Maecker Holden , Langelier Charles R. , Steen Hanno , Altman Matthew C. , Montgomery Ruth R. , Levy Ofer , Melamed Esther , Pulendran Bali , Diray-Arce Joann , Smolen Kinga K. , Fragiadakis Gabriela K. , Becker Patrice M. , Augustine Alison D. , Sekaly Rafick P. , Ehrlich Lauren I. R. , Fourati Slim , Peters Bjoern , Kleinstein Steven H. , Guan Leying
Published: November 2023

Hospitalized COVID-19 patients exhibit diverse clinical outcomes, with some individuals diverging over time even though their initial disease severity appears similar. A systematic evaluation of molecular and cellular profiles over the full disease course can link immune programs and their coordination with progression heterogeneity. In this study, we carried out deep immunophenotyping and conducted longitudinal multi-omics modeling integrating ten distinct assays on a total of 1,152 IMPACC participants and identified several immune cascades that were significant drivers of differential clinical outcomes. Increasing disease severity was driven by a temporal pattern that began with the early upregulation of immunosuppressive metabolites and then elevated levels of inflammatory cytokines, signatures of coagulation, NETosis, and T-cell functional dysregulation. A second immune cascade, predictive of 28-day mortality among critically ill patients, was characterized by reduced total plasma immunoglobulins and B cells, as well as dysregulated IFN responsiveness. We demonstrated that the balance disruption between IFN-stimulated genes and IFN inhibitors is a crucial biomarker of COVID-19 mortality, potentially contributing to the failure of viral clearance in patients with fatal illness. Our longitudinal multi-omics profiling study revealed novel temporal coordination across diverse omics that potentially explain disease progression, providing insights that inform the targeted development of therapies for hospitalized COVID-19 patients, especially those critically ill.
Voltage-gated T-type calcium channel blockers reduce apoptotic body mediated SARS-CoV-2 cell-to-cell spread and subsequent cytokine storm
Authors: Phan Thanh Kha , Sheerin Dylan , Shi Bo , Dayton Merle , Mackewicz Liana , Ozkocak Dilara C. , Atkin-Smith Georgia , Peton Nashied , Audi Omar , Tixeira Rochelle , Ashdown George , Davidson Kathryn C. , Doerflinger Marcel , Coussens Anna K. , Poon Ivan K. H.
Published: November 2023

SARS-CoV-2 typically utilises host angiotensin-converting enzyme 2 (ACE2) as a cellular surface receptor and host serine protease TMPRSS2 for the proteolytic activation of viral spike protein enabling viral entry. Although macrophages express low levels of ACE2, they are often found positive for SARS-CoV-2 in autopsied lungs from COVID-19 patients. As viral-induced macrophage inflammation and overwhelming cytokine release are key immunopathological events that drives exacerbated tissue damage in severe COVID-19 patients, insights into the entry of SARS-CoV-2 into macrophages are therefore critical to understand COVID-19 pathogenesis and devise novel COVID-19 therapies. Mounting evidence suggest that COVID-19 pathogenesis is associated with apoptosis, a type of programmed cell death that often leads to the release of numerous large extracellular vesicles (EVs) called apoptotic bodies (ApoBDs). Here, we showed that ApoBDs derived from SARS-CoV-2-infected cells carry viral antigens and infectious virions. Human monocyte-derived macrophages readily efferocytosed SARS-CoV-2-induced ApoBDs, resulting in SARS-CoV-2 entry and pro-inflammatory responses. To target this novel ApoBD-mediated viral entry process, we screened for ApoBD formation inhibitors and discovered that T-type voltage-gated calcium channel (T-channel) blockers can inhibit SARS-CoV-2-induced ApoBD formation. Mechanistically, T-channel blockers impaired the extracellular calcium influxes required for ApoBD biogenesis. Importantly, blockade of ApoBD formation by T-channel blockers were able to limit viral dissemination and virus-induced macrophage inflammationin vitroand in a pre-clinical mouse model of severe COVID-19. Our discovery of the ApoBD-efferocytosis-mediated viral entry reveals a novel route for SARS-CoV-2 infection and cytokine storm induction, expanding our understanding of COVID-19 pathogenesis and offering new therapeutic avenues for infectious diseases.
Do more food choices lead to bad decisions? A case study in predacious ladybird beetle,Propylea dissecta
Authors: Verma Lata , Mishra Geetanjali , Omkar
Published: November 2023

Understanding why animals choose one food over another is one of the key questions underlying the fields of behaviour ecology. This study aims to test if ladybird beetles,Propylea dissectaMulsant (Coleoptera: Coccinellidae) can forage selectively for nutrients in order to redress specific nutritional imbalances to maximise their fitness. The general approach was, first, to manipulate the nutritional status of the predator by rearing them in five separate pre-treatment dietary groups from first instar larvae to newly emerged adult stage. Thereafter, we tested their feeding response to five different types of food, i.e.,Aphis craccivoraKoch,Aphis neriiBoyer de Fonsclombe, conspecific eggs, heterospecific eggs and mixed pollen grains, equidistantly placed in Petri dish. On the basis of newly emerged adults’ food choice, they were reared on the same diet for 10 days. Thereafter, adults were paired with their opposite sex (collected from stock culture reared onA.craccivora) and mating and reproductive parameters were recorded. Our results suggested that the variety of food did not affect the preference of ladybird beetle,P. dissecta. They tend to choose their natural diet,i.e., aphid in each dietary regime. We found that previous dietary regime significantly influences the mating and reproductive parameters of both the male and female except for the time to commence mating by the male. Food choices of adult beetles were found to significantly influence the time to commence mating, average fecundity and percent egg viability in males and the mating duration in females.
Activated NK Cells with Pro-inflammatory Features are Associated with Atherogenesis in Perinatally HIV-Acquired Adolescents
Authors: Alles Mario , Gunasena Manuja , Kettelhut Aaren , Ailstock Kate , Musiime Victor , Kityo Cissy , Richardson Brian , Mulhern Will , Tamilselvan Banumathi , Rubsamen Michael , Kasturiratna Dhanuja , Demberg Thorsten , Cameron Cheryl M. , Cameron Mark J. , Dirajlal-Fargo Sahera , Funderburg Nicholas T. , Liyanage Namal P.M.
Published: November 2023

Human immunodeficiency virus (HIV) is associated with persistent immune activation and dysfunction in people with HIV despite treatment with antiretroviral therapy (ART). Modulation of the immune system may be driven by: low-level HIV replication, co-pathogens, gut dysbiosis /translocation, altered lipid profiles, and ART toxicities. In addition, perinatally acquired HIV (PHIV) and lifelong ART may alter the development and function of the immune system. Our preliminary data and published literature suggest reprogramming innate immune cells may accelerate aging and increase the risk for future end-organ complications, including cardiovascular disease (CVD). The exact mechanisms, however, are currently unknown. Natural killer (NK) cells are a highly heterogeneous cell population with divergent functions. They play a critical role in HIV transmission and disease progression in adults. Recent studies suggest the important role of NK cells in CVDs; however, little is known about NK cells and their role in HIV-associated cardiovascular risk in PHIV adolescents. Here, we investigated NK cell subsets and their potential role in atherogenesis in PHIV adolescents compared to HIV-negative adolescents in Uganda. Our data suggest, for the first time, that activated NK subsets in PHIV adolescents may contribute to atherogenesis by promoting plasma oxidized low-density lipoprotein (Ox-LDL) uptake by vascular macrophages.
HDL Particle Concentration and Size Predict Incident Coronary Artery Disease Events in People with Type 1 Diabetes
Authors: Costacou Tina , Vaisar Tomas , Miller Rachel G. , Davidson W. Sean , Heinecke Jay W. , Orchard Trevor J. , Bornfeldt Karin E.
Published: November 2023

Background

Cholesterol efflux capacity (CEC) negatively correlates with cardiovascular disease risk. Small HDL particles account almost quantitively for CEC, perhaps mediated through efflux of outer leaflet plasma membrane phospholipids by ABCA1. People with type 1 diabetes (T1D) are at increased risk of coronary artery disease (CAD) despite normal levels of HDL-cholesterol (HDL-C). We therefore tested the hypotheses that small HDL particles (HDL-P)—rather than HDL-C levels—predict incident CAD in T1D.

Methods

Incident CAD (CAD death, myocardial infarction, and/or coronary revascularization) was determined in a cohort of 550 participants with childhood-onset T1D. HDL-P was quantified by calibrated ion mobility analysis. CEC and phospholipid efflux were quantified with validated assays.

Results

During a median follow-up of 26 years, 36.5% of the participants developed incident CAD. In multivariable Cox models, levels of HDL-C and apolipoprotein A-I (APOA1) did not predict CAD risk. In contrast, extra-small HDL particle levels strongly and negatively predicted risk (hazard ratio [HR]=0.25, 95% confidence interval [CI]=0.13–0.49). An increased concentration of total HDL particles (T-HDL-P) (HR=0.87, CI=0.82–0.92) and three other HDL sizes were weaker predictors of risk: small HDL (HR=0.80, 0.65-0.98), medium HDL (HR=0.78, CI=0.70–0.87) and large HDL (HR=0.72, CI=0.59–0.89). Although CEC negatively associated with incident CAD, that association disappeared after the model was adjusted for T-HDL-P. Isolated small HDLs strongly promoted ABCA1-dependent efflux of membrane outer leaflet phospholipids.

Conclusions

Low concentrations of T-HDL-P and all four sizes of HDL subpopulations predicted incident CAD independently of HDL-C, APOA1, and other common CVD risk factors. Extra-small HDL was a much stronger predictor of risk than the other HDLs. Our data are consistent with the proposal that small HDLs play a critical role in cardioprotection in T1D, which might be mediated by macrophage plasma membrane outer leaflet phospholipid export and cholesterol efflux by the ABCA1 pathway.
Muscle mitochondrial bioenergetic capacities is associated with multimorbidity burden in older adults: the Study of Muscle, Mobility and Aging (SOMMA)
Authors: Mau Theresa , Blackwell Terri L. , Cawthon Peggy M. , Molina Anthony J. A. , Coen Paul M. , Distefano Giovanna , Kramer Philip A. , Ramos Sofhia V. , Forman Daniel E. , Goodpaster Bret H. , Toledo Frederico G. S. , Duchowny Kate A. , Sparks Lauren M. , Newman Anne B. , Kritchevsky Stephen B. , Cummings Steven R.
Published: November 2023

Background

The geroscience hypothesis posits that aging biological processes contribute to many age-related deficits, including the accumulation of multiple chronic diseases. Though only one facet of mitochondrial function, declines in muscle mitochondrial bioenergetic capacities may contribute to this increased susceptibility to multimorbidity.

Methods

The Study of Muscle, Mobility and Aging (SOMMA) assessedex vivomuscle mitochondrial energetics in 764 older adults (mean age =76.4, 56.5% women, 85.9% non-Hispanic white) by high-resolution respirometry of permeabilized muscle fibers. We estimated the proportional odds ratio (POR [95%CI]) for the likelihood of greater multimorbidity (four levels: 0 conditions, N=332; 1 condition, N=299; 2 conditions, N=98; or 3+ conditions, N=35) from an index of 11 conditions, per SD decrement in muscle mitochondrial energetic parameters. Distribution of conditions allowed for testing the associations of maximal muscle energetics with some individual conditions.

Results

Lower oxidative phosphorylation supported by fatty acids and/or complex-I and -II linked carbohydrates (e.g., Max OXPHOSCI+CII) was associated with a greater multimorbidity index score (POR=1.32[1.13,1.54]) and separately with diabetes mellitus (OR=1.62[1.26,2.09]), depressive symptoms (OR=1.45[1.04,2.00]) and possibly chronic kidney disease (OR=1.57[0.98,2.52]) but not significantly with other conditions (e.g., cardiac arrhythmia, chronic obstructive pulmonary disease).

Conclusions

Lower muscle mitochondrial bioenergetic capacities was associated with a worse composite multimorbidity index score. Our results suggest that decrements in muscle mitochondrial energetics may contribute to a greater global burden of disease and is more strongly related to some conditions than others.(Words= 233)