bluuebunny/crossref_metadata_2025 huggingface dataset:
Elevated HIV Viral Load is Associated with Higher Recombination Rate In Vivo
Authors: Romero Elena V , Feder Alison F
Published: January 2024

HIV’s exceptionally high recombination rate drives its intrahost diversification, enabling immune escape and multidrug resistance within people living with HIV. While we know that HIV’s recombination rate varies by genomic position, we have little understanding of how recombination varies throughout infection or between individuals as a function of the rate of cellular coinfection. We hypothesize that denser intrahost populations may have higher rates of coinfection and therefore recombination. To test this hypothesis, we develop a new approach (recombination analysis via time series linkage decay or RATS-LD) to quantify recombination using autocorrelation of linkage between mutations across time points. We validate RATS-LD on simulated data under short read sequencing conditions and then apply it to longitudinal, high-throughput intrahost viral sequencing data, stratifying populations by viral load (a proxy for density). Among sampled viral populations with the lowest viral loads (<26,800 copies/mL), we estimate a recombination rate of 1.5×10−5 events/bp/generation (95% CI: 7×10−6 to 2.9×10−5), similar to existing estimates. However, among samples with the highest viral loads (>82,000 copies/mL), our median estimate is approximately 6 times higher. In addition to co-varying across individuals, we also find that recombination rate and viral load are associated within single individuals across different time points. Our findings suggest that rather than acting as a constant, uniform force, recombination can vary dynamically and drastically across intrahost viral populations and within them over time. More broadly, we hypothesize that this phenomenon may affect other facultatively asexual populations where spatial co-localization varies.
LINE-1 mRNA 3′ end dynamics shape its biology and retrotransposition potential
Authors: Janecki Damian M , Sen Raneet , Szóstak Natalia , Kajdasz Arkadiusz , Kordyś Martyna , Plawgo Kinga , Pandakov Dmytro , Philips Anna , Warkocki Zbigniew
Published: January 2024

LINE-1 (L1) retrotransposons are mobile genetic elements that create new genomic insertions by a copy-paste mechanism involving L1 RNA/RNP intermediates. L1 encodes two ORFs, of which L1-ORF2p nicks genomic DNA and reverse transcribes L1 mRNA using the nicked DNA as a primer which base-pairs with poly(A) tail of L1 mRNA. To better understand the importance of non-templated L1 3′ ends’ dynamics and the interplay between L1 3′ and 5′ ends, we investigated the effects of genomic knock-outs and temporal knock-downs of XRN1, DCP2, and other factors. We hypothesized that in the absence of XRN1, the major 5′→3′ exoribonuclease, there would be more L1 mRNA and retrotransposition. Conversely, we observed that loss of XRN1 decreased L1 retrotransposition. This occurred despite slight stabilization of L1 mRNA, but with decreased L1 RNP formation. Similarly, loss of DCP2, the catalytic subunit of the decapping complex, lowered retrotransposition despite increased steady-state levels of L1 proteins. In both XRN1 and DCP2 depletions we observed shortening of L1 3′ poly(A) tails and their increased uridylation by TUT4/7. We explain the observed reduction of L1 retrotransposition by the changed qualities of non-templated L1 mRNA 3′ ends demonstrating the important role of L1 3′ end dynamics in L1 biology.
Minimization of the E. coli ribosome, aided and optimized by community science
Authors: Tangpradabkul Tiyaporn , Palo Michael , Townley Jill , Hsu Kenneth B , participants Eterna , Smaga Sarah , Das Rhiju , Schepartz Alanna
Published: January 2024

The ribosome is a ribonucleoprotein complex found in all domains of life. Its role is to catalyze protein synthesis, the messenger RNA (mRNA)-templated formation of amide bonds between α-amino acid monomers. Amide bond formation occurs within a highly conserved region of the large ribosomal subunit known as the peptidyl transferase center (PTC). Here we describe the step-wise design and characterization of mini-PTC 1.1, a 284-nucleotide RNA that recapitulates many essential features of the Escherichia coli PTC. Mini-PTC 1.1 folds into a PTC-like structure under physiological conditions, even in the absence of r-proteins, and engages small molecule analogs of A- and P-site tRNAs. The sequence of mini-PTC 1.1 differs from the wild type E. coli ribosome at 12 nucleotides that were installed by a cohort of citizen scientists using the on-line video game Eterna. These base changes improve both the secondary structure and tertiary folding of mini-PTC 1.1 as well as its ability to bind small molecule substrate analogs. Here, the combined input from Eterna citizen-scientists and RNA structural analysis provides a robust workflow for the design of a minimal PTC that recapitulates many features of an intact ribosome.
The Making of Corporate Legal Concession Theory
Authors: Hardman Jonathan
Published: January 2024

Professor Watson’s The Making of the Modern Company traces the development of the modern corporate form back to the East India Company, disproving a common notion that company law originated solely with small, private companies. This review article argues three key implications of this excellent book. First, Watson focuses on the duality of the modern company—with state-provided and private features. This cuts through, and goes a long way to resolving, the ongoing historic debate as to the nature of the company. Second, the primary unit of study chosen—the modern company—reminds corporate lawyers of our role in studying this duality in a very crowded field. Third, despite eschewing ‘concession theories’ of company law (which hold that the company is merely a concession from the state), Watson demonstrates a role for the state in the modern company that is often overlooked.
Sequential Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor-Induced Radical Surgery in Oligometastatic Non–Small Cell Lung Cancer: A Case Report
Authors: Wang Huaiyu , Fan Zaiwen , Yang Xiaoming , Wu Qing , Jiang Suxin , Zhu Jingna , Liu Jie , Zhou Chuanhong , Liu Yinghui , You Xia , Han Yong
Published: January 2024

Sequential regimens in patients with epidermal growth factor receptor (EGFR) mutation-positive non–small cell lung cancer (NSCLC) can overcome tyrosine kinase inhibitor (TKI) resistance and maximize clinical benefit. Patients with advanced NSCLC can achieve excellent tumor control after a period of EGFR-TKI treatment. Patients may benefit from additional local treatment, such as surgery or radiation therapy, once the tumor is under control. Here, we present a case of a patient with advanced oligometastatic NSCLC with EGFR mutations who achieved downstaging through sequential EGFR-TKI-based precision medicine allowing resection of residual disease.
Upland Sandpipers select for later time since fire and experience high nest survival in grasslands managed with patch-burn grazing
Authors: Rischette Alexander C , Geaumont Benjamin A , Duquette Cameron A , Hovick Torre J
Published: January 2024

Upland Sandpipers (Bartramia longicauda) are a grassland obligate shorebird that nests in dense vegetation structure near recently disturbed areas and could benefit from management practices that promote heterogenous vegetation structure. Upland Sandpipers primary breeding range is generally managed for livestock production using traditional practices that lack patchy disturbances to facilitate higher levels of structural heterogeneity. Patch-burn grazing (PBG) could be an alternative management practice for Upland Sandpiper conservation for its use to create areas of dense vegetation structure near recently disturbed areas. However, limited information is available regarding nest production of Upland Sandpipers within a PBG framework. To assess the compatibility of PBG with Upland Sandpiper conservation, we estimated nest site selection and survival of Upland Sandpiper nests on private lands managed with PBG in the unglaciated plains region of North Dakota. We located 59 nests from 2017 to 2020. Upland Sandpipers avoided 1 year since fire (YSF) patches and selected for 2 and 3 YSF patches for nest sites. Additionally, nest site selection decreased with increased bare ground and at intermediate distances to the nearest Upland Sandpiper nest. Upland Sandpipers experienced high overall nest survival during the study with 51 of 59 nests successfully hatching, which limited our ability to make inferences between daily survival rates and variables of interest. Our findings suggest that PBG can provide suitable nesting cover for Upland Sandpipers in later YSF patches despite annual prescribed fire and livestock grazing during the nesting season. PBG seems a suitable grassland management strategy that should be included in conservation planning within Upland Sandpiper’s breeding distribution.
Maize requires Embryo defective27 for embryogenesis and seedling development
Authors: Liu Xin-Yuan , Jiang Rui-Cheng , Ma Bing , Wang Yong , Yang Yan-Zhuo , Xu Chunhui , Sun Feng , Tan Bao-Cai
Published: January 2024

The essential role of plastid translation in embryogenesis has been established in many plants, but a retrograde signal triggered by defective plastid translation machinery that may leads to embryogenesis arrest remains unknown. In this study, we characterized an embryo defective27 (emb27) mutant in maize (Zea mays), and cloning indicates that Emb27 encodes the plastid ribosomal protein S13. The null mutant emb27-1 conditions an emb phenotype with arrested embryogenesis; however, the leaky mutant emb27-2 exhibits normal embryogenesis but an albino seedling-lethal phenotype. The emb27-1/emb27-2 trans-heterozygotes display varying phenotypes from emb to normal seeds but albino seedlings. Analysis of the Emb27 transcription levels in these mutants revealed that the Emb27 expression level in the embryo corresponds with the phenotypic expression of the emb27 mutants. In the W22 genetic background, an Emb27 transcription level higher than 6% of the wild-type level renders normal embryogenesis, whereas lower than that arrests embryogenesis. Mutation of Emb27 reduces the level of plastid 16S rRNA and the accumulation of the plastid-encoded proteins. As a secondary effect, splicing of several plastid introns was impaired in emb27-1 and 2 other plastid translation-defective mutants, emb15 and emb16, suggesting that plastome-encoded factors are required for the splicing of these introns, such as Maturase K (MatK). Our results indicate that EMB27 is essential for plastid protein translation, embryogenesis, and seedling development in maize and reveal an expression threshold of Emb27 for maize embryogenesis.
COVID-19 susceptibility, hospitalization and severity and the risk of brain cortical structure: a Mendelian randomization study
Authors: Sun D , Shi Z , Chen H , Du Q , Zhang Y , Wang R , Kong L , Luo W , Lang Y , Wang X , Zhou H
Published: January 2024

Background

Observational studies have reported structural changes in the brains of patients with coronavirus disease 2019 (COVID-19); it remains unclear whether these associations are causal.

Aim

We evaluated the causal effects of COVID-19 susceptibility, hospitalization and severity on cortical structures.

Design

Mendelian randomization (MR) study.

Methods

Data on the different COVID-19 phenotypes were obtained from the latest large-scale genome-wide association study (R7) of the COVID-19 Host Genetics Initiative. Brain structure data, including cortical thickness (TH) and surface area (SA), were obtained from the ENIGMA Consortium. Additionally, we employed the round 5 dataset released in January 2021 as the validation cohort. The inverse-variance weighted (IVW) method was used as the primary analysis in MR. Sensitivity analyses were conducted to evaluate heterogeneity and pleiotropy. We performed enrichment analysis on the MR analyses that passed the sensitivity analysis filtering.

Results

After IVW and sensitivity analyses, we observed causal associations between COVID-19 susceptibility and rostral middle frontal SAw (P = 0.0308, β = −39.1236), cuneus THw (P = 0.0170, β = −0.0121), medial orbitofrontal THw (P = 0.0002, β = 0.0225), postcentral THw (P = 0.0217, β = −0.0106), temporal pole THw (P = 0.0077, β = 0.0359), medial orbitofrontal SAnw (P = 0.0106, β = −24.0397), medial orbitofrontal THnw (P = 0.0007, β = 0.0232), paracentral SAnw (P = 0.0483, β = −20.1442), rostral middle frontal SAnw (P = 0.0368, β = −81.9719) and temporal pole THnw (P = 0.0429, β = 0.0353). COVID-19 hospitalization had causal effects on medial orbitofrontal THw (P = 0.0053, β = 0.0063), postcentral THw (P = 0.0143, β = −0.0042), entorhinal THnw (P = 0.0142, β = 0.0142), medial orbitofrontal THnw (P = 0.0147, β = 0.0065) and paracentral SAnw (P = 0.0119, β = −7.9970). COVID-19 severity had causal effects on rostral middle frontal SAw (P = 0.0122, β = −11.8296), medial orbitofrontal THw (P = 0.0155, β = 0.0038), superior parietal THw (P = 0.0291, β = −0.0021), lingual SAnw (P = 0.0202, β = −11.5270), medial orbitofrontal THnw (P = 0.0290, β = 0.0039), paracentral SAnw (P = 0.0180, β = −5.7744) and pars triangularis SAnw (P = 0.0151, β = −5.4520).

Conclusion

Our MR results demonstrate a causal relationship between different COVID-19 phenotypes and cortical structures.
Radiation dose to breast during digital mammography in Tanzania
Authors: Edmund Elisha , Kamuzora Mary , Muhogora Wilbroad , Ngoya Patrick , Muhulo Alex , Amirali Assad , Makoba Atumaini , Ngoye Wilson , Ngaile Justin , Majatta Salma , Ngulimi Miguta , Mwambinga Salome , Kaijage Tunu
Published: January 2024

The aim of this study was to evaluate the mean glandular dose (MGD), to assess the potential for optimization, and to propose diagnostic reference levels (DRLs). MGD was estimated from air kerma measurements and patient information collected during mammography examinations. The 75th percentile values were determined as the third quartile of the median MGD values for all hospitals, and DRLs set as 75th percentile of MGD values. The estimated median values of MGD ranged from 1.5 to 3.9 mGy for craniocaudal projection for median range of 15–59 mm compressed breast thickness (CBT). For a CBT range of 15–63 mm, the median MGD value was 1.5–5.1 mGy for medio-lateral oblique projection. Comparison with other studies showed that the MGD values obtained in this study were relatively high. The magnitude and wide variation of the exposure parameters suggest existing potential for optimization. The training of radiology staff was identified as a top priority.
The effect of cooling rate on the precision of measurement of glow peak 5 in the thermoluminescence of LiF:Mg,Ti (TLD-100)
Authors: Bokobza Yogev , Biderman Shlomo , Horowitz Yigal Shalom , Oster Leonid , Eliyahu Ilan , Shapiro Alex , Nemirovsky Dmitry , Reshes Galina , Herman Beny , Einav Hezy
Published: January 2024

The effect of natural rapid cooling and oven slow cooling on the precision of thermoluminescence measurements of LiF:Mg,Ti is investigated. Three separate series of measurements resulted in average precisions of 5.1 and 5.0%, respectively. However, the highest precision of 1.7% (1 SD) was achieved for an oven-cooled material.
Navigating the multiple views of value in assessing public procurement
Authors: Merisalo Maria , Hyytinen Kirsi , Oksanen Juha , Pihlajamaa Matti , Uyarra Elvira
Published: January 2024

Public procurement has gained a heightened role in responding to grand societal challenges. Additional goals besides the more traditional objectives for public procurement have produced conflicts and raised the question of how to assess public procurement comprehensively. In this article, we explore the impact model created for the National Public Procurement Strategy of Finland. We investigate the main positions from where to value and assess public procurement and the key conflicts between the different positions. The national strategy of Finland emphasizes that public organizations should put more weight on secondary policy goals. However, this seems to produce “paradoxes,” as partly contradicting goals are pursued simultaneously. The article shows that it is possible to highlight both the strategic and operational roles of public procurement. However, the existence of the paradoxes is important to take into account in governing public procurement.
Outpatient Clinics, Visiting Nurses and Propaganda: Spaces, Actors and Tools of Mental Hygiene in Interwar Italy
Authors: Scarfone Marianna
Published: January 2024

In interwar Italy, the mental hygiene movement enacted a series of measures in order to control, prevent and contain psychiatric diseases. Developing as a pillar of social medicine, mental hygiene represented a challenging outlook for the psychiatric field, as far as it filled a gap in existing assistance, providing outpatient facilities and avoiding the pitfalls of hospitalisation’s legal constraints. This article analyses the debates aimed at reforming the 1904 law on asylums and the issues at stake, as autonomy from judiciary powers and screening and follow-up in free consultations. It then examines the functioning of dispensaries that responded to these issues, the role of the visiting nurses, as well as that of propaganda deployed by the local sections of The League of Mental Hygiene. Relying on diverse case studies, it aims at reopening the debate on a controversial phase of Italian sociopolitical history through the analysis of psychiatric practices.
Physiological, metabolic and hormonal responses of two Pinus spp. with contrasting susceptibility to brown-spot needle blight disease
Authors: Monteiro Pedro , Valledor Luis , Osorio Sonia , Camisón Álvaro , Vallarino José Gabriel , Gómez-Cadenas Aurelio , Díez Julio Javier , Pinto Glória
Published: January 2024

Needle blights are serious fungal diseases affecting European natural and planted pine forests. Brown-spot needle blight (BSNB) disease, caused by the fungus Lecanosticta acicola, causes canopy defoliation and severe productivity losses, with consequences depending on host susceptibility. To gain new insights into BSNB plant–pathogen interactions, constitutive and pathogen-induced traits were assessed in two host species with differential disease susceptibility. Six-month-old Pinus radiata D. Don (susceptible) and Pinus pinea L. (more resistant) seedlings were needle inoculated with L. acicola under controlled conditions. Eighty days after inoculation, healthy-looking needles from symptomatic plants were assessed for physiological parameters and sampled for biochemical analysis. Disease progression, plant growth, leaf gas-exchanges and biochemical parameters were complemented with hormonal and untargeted primary metabolism analysis and integrated for a holistic analysis. Constitutive differences between pine species were observed. Pinus pinea presented higher stomatal conductance and transpiration rate and higher amino and organic acids, abscisic acid as well as putrescine content than P. radiata. Symptoms from BSNB disease were observed in 54.54% of P. radiata and 45.45% of P. pinea seedlings, being more pronounced and generalized in P. radiata. For both species, plant height, sub-stomatal CO2 concentration and water-use efficiency were impacted by infection. In P. radiata, total soluble sugars, starch and total flavonoids content increased after infection. No differences in hormone content after infection were observed. However, secondary metabolism was induced in P. pinea visible through total phenolics, flavonoids and putrescine accumulation. Overall, the observed results suggest that P. pinea constitutive and induced traits may function as two layers of a defence strategy which contributed to an increased BSNB resistance in comparison with P. radiata. This is the first integrative study linking plant physiological and molecular traits in Pinus–Lecanosticta acicola pathosystem, contributing to a better understanding of the underlying resistance mechanisms to BSNB disease in pines.
Facial Beauty and the Correlation of Associated Attributes: An Empirical Aesthetic Database Study
Authors: Singh Prateush , Birkett Liam , Dhar Shivani , Krumhuber Eva , Mosahebi Afshin , Ponniah Allan
Published: January 2024

Background:

The pursuit of understanding facial beauty has been the subject of scientific interest since time immemorial. How beauty is associated with other perceived attributes that affect human interaction remains elusive. This article aims to explore how facial attractiveness correlates with health, happiness, femininity, and perceived age. We review the existing literature and report an empirical study using expert raters.

Methods:

A peer-reviewed database of 2870 aesthetic female faces with a global ethnic distribution was created. Twenty-one raters were asked to score frontal images on the attributes of health, happiness, femininity, perceived age, and attractiveness, on a Likert scale of 0–100.

Results:

Pearson correlation coefficients (“r”) were calculated to correlate attributes, with multiple regression analyses and P values calculated. Strong positive correlation was found between attractiveness and health (r = 0.61, P < 0.05), attractiveness and femininity (r = 0.7, P < 0.05), and health and femininity (r = 0.57, P < 0.05); medium positive correlation between health and happiness (r = 0.31, P < 0.05); and small positive correlation between happiness and femininity (r = 0.21, P < 0.05). A neutral relationship was observed between perceived age and happiness (0.01, P = 0.75), and medium negative correlation between perceived age and attractiveness (−0.32, P < 0.05), health (−0.36, P < 0.05), and femininity (−0.31, P < 0.05).

Conclusions:

Our study illustrates a positive correlation between the positive attributes of health, happiness, femininity and attractiveness, with a negative correlation of all characteristics with increasing perceived age. This provides insight into the complexity of human interaction and provides a holistic view of attraction as being a gateway to the reflexive perception of other attributes. The implications encourage an aesthetic focus on facial reconstruction.
Use of Supinator Motor Branches in Targeted Muscle Reinnervation of the Superficial Radial Nerve
Authors: Ferrin Peter C. , Hathaway Brynn , Russo Stephanie A. , Peters Blair R.
Published: January 2024

Symptomatic neuromas of the superficial radial nerve (SRN) can cause debilitating pain. Traditional surgical management options have demonstrated inconsistent outcomes prompting a search for alternatives. Recent reports have emerged on the use of targeted muscle reinnervation (TMR) for neuromas of the SRN using donors that are well established in hand surgery, such as the brachioradialis (BR) or extensor capri radialis longus or brevis. Use of the brachioradialis or extensor capri radialis longus motor targets can require surgery at or above the level of the antecubital fossa, and denervation of these muscle groups may be undesirable in cases of complex upper extremity injury where these donors may be needed for tendon or nerve transfer. The supinator is an expendable and often overlooked donor nerve that has not been assessed as a target for TMR of the SRN. In this case series, three patients with SRN neuromas whose conservative management failed and who did not have an SRN lesion amenable to reconstruction were managed with TMR to the nerves to supinator. At latest follow-up (9–22 months), no patients had deficits in supination or evident donor site morbidity. Two patients reported complete resolution of their SRN neuroma pain, and one patient reported partial improvement. This case series reports early results of TMR of the SRN using nerves to supinator in cases of SRN neuromas not amenable to reconstruction, demonstrating technical feasibility, improvements in neuroma pain, and no discernible donor morbidity.
Prepectoral and Retropectoral Breast-implant–Associated Anaplastic Large-cell Lymphoma
Authors: Ziegler-Rodriguez Gonzalo , Garces-Ruiz Milko , De La Cruz-Ku Gabriel , Ziegler-Rodriguez Otto , Ziegler-Gutierrez Otto , Garces-Castre Milko , Montes-Gil Jaime , Neira Jimena , Taxa-Rojas Luis , Cebrian Rosa , Chatterjee Abhishek
Published: January 2024

Breast-implant–associated anaplastic large cell lymphoma (BIA-ALCL) is a non-Hodgkin lymphoma that arises in the space between the surface of a breast implant and the fibrous capsule that grows around the implant. Since its first description 20 years ago, almost 1000 cases of BIA-ALCL have been diagnosed worldwide. Nowadays, guidelines describe the diagnosis, staging, and treatment of this disease. We present the first two cases diagnosed and treated in Peru, demonstrating a wide range of aggressiveness of BIA-ALCL.
Consequence of Antivirals Versus Standard Care on Clinical Situation in Patients With COVID-19
Authors: Alsaraj Marwa N. , Qazzaz Mohannad E. , Abed Mohammed N. , Alassaf Fawaz A. , Alfahad Mohanad A. , Jasim Mahmood H.M.
Published: January 2024

Favipiravir and remdesivir have recently received more clinical interest for the management of COVID-19. The study aimed to explore the effectiveness of favipiravir or remdesivir on the clinical outcome of SARS-CoV-2 patients in comparison with standard care. All patients were given standard care before being randomized into the following 3 groups: standard care group (standard care only), remdesivir group (remdesivir and standard care), and favipiravir group (group 3, favipiravir and standard care). The primary endpoint of the study was time to recovery or the clinical condition of patients on day 14. A total of 156 patients underwent randomization (53 assigned to standard care group, 51 to favipiravir group, and 52 to remdesivir group). The percentage of death in favipiravir and remdesivir groups was higher than those in the standard care group and likewise the liver enzymes. Studying the time to starting therapy showed that early administration of antivirals resulted in lower percentage of mortality. The ratio of hazard for early favipiravir and remdesivir was lower in comparison with those treated with late administration of the same drugs (hazard ratio, 0.62; 95% confidence interval [CI], 0.62–0.73 vs 3.22; 95% CI, 3.21–3.44, respectively, for favipiravir and 0.11; 95% CI, 0.10–0.12 vs 3.44; 95% CI, 3.43–3.55, respectively, for remdesivir). For favipiravir or remdesivir to have more beneficial effects than standard care alone for SARS-CoV-2 patients, they need to be started as early as possible. However, regular monitoring of liver function is required.
Patient engagement in designing, conducting, and disseminating clinical pain research: IMMPACT recommended considerations
Authors: Haroutounian Simon , Holzer Katherine J. , Kerns Robert D. , Veasley Christin , Dworkin Robert H. , Turk Dennis C. , Carman Kristin L. , Chambers Christine T. , Cowan Penney , Edwards Robert R. , Eisenach James C. , Farrar John T. , Ferguson McKenzie , Forsythe Laura P. , Freeman Roy , Gewandter Jennifer S. , Gilron Ian , Goertz Christine , Grol-Prokopczyk Hanna , Iyengar Smriti , Jordan Isabel , Kamp Cornelia , Kleykamp Bethea A. , Knowles Rachel L. , Langford Dale J. , Mackey Sean , Malamut Richard , Markman John , Martin Kathryn R. , McNicol Ewan , Patel Kushang V. , Rice Andrew S.C. , Rowbotham Michael , Sandbrink Friedhelm , Simon Lee S. , Steiner Deborah J. , Vollert Jan
Published: January 2024

In the traditional clinical research model, patients are typically involved only as participants. However, there has been a shift in recent years highlighting the value and contributions that patients bring as members of the research team, across the clinical research lifecycle. It is becoming increasingly evident that to develop research that is both meaningful to people who have the targeted condition and is feasible, there are important benefits of involving patients in the planning, conduct, and dissemination of research from its earliest stages. In fact, research funders and regulatory agencies are now explicitly encouraging, and sometimes requiring, that patients are engaged as partners in research. Although this approach has become commonplace in some fields of clinical research, it remains the exception in clinical pain research. As such, the Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials convened a meeting with patient partners and international representatives from academia, patient advocacy groups, government regulatory agencies, research funding organizations, academic journals, and the biopharmaceutical industry to develop consensus recommendations for advancing patient engagement in all stages of clinical pain research in an effective and purposeful manner. This article summarizes the results of this meeting and offers considerations for meaningful and authentic engagement of patient partners in clinical pain research, including recommendations for representation, timing, continuous engagement, measurement, reporting, and research dissemination.
Behavioral characterization of G-protein-coupled receptor 160 knockout mice
Authors: Schafer Rachel M. , Giancotti Luigino A. , Davis Daniel J. , Larrea Ivonne G. , Farr Susan A. , Salvemini Daniela
Published: January 2024

Neuropathic pain is a devastating condition where current therapeutics offer little to no pain relief. Novel nonnarcotic therapeutic targets are needed to address this growing medical problem. Our work identified the G-protein-coupled receptor 160 (GPR160) as a potential target for therapeutic intervention. However, the lack of small-molecule ligands for GPR160 hampers our understanding of its role in health and disease. To address this void, we generated a global Gpr160 knockout (KO) mouse using CRISPR-Cas9 genome editing technology to validate the contributions of GPR160 in nociceptive behaviors in mice. Gpr160 KO mice are healthy and fertile, with no observable physical abnormalities. Gpr160 KO mice fail to develop behavioral hypersensitivities in a model of neuropathic pain caused by constriction of the sciatic nerve. On the other hand, responses of Gpr160 KO mice in the hot-plate and tail-flick assays are not affected. We recently deorphanized GPR160 and identified cocaine- and amphetamine-regulated transcript peptide (CARTp) as a potential ligand. Using Gpr160 KO mice, we now report that the development of behavioral hypersensitivities after intrathecal or intraplantar injections of CARTp are dependent on GPR160. Cocaine- and amphetamine-regulated transcript peptide plays a role in various affective behaviors, such as anxiety, depression, and cognition. There are no differences in learning, memory, and anxiety between Gpr160 KO mice and their age-matched and sex-matched control floxed mice. Results from these studies support the pronociceptive roles of CARTp/GPR160 and GPR160 as a potential therapeutic target for treatment of neuropathic pain.
Factors Influencing Antihypertensive Medication Adherence Among Historically Underrepresented Adults
Authors: Kokenge Molly C. , Ruppar Todd M.
Published: January 2024

Background

Addressing disparities in blood pressure control must include supporting antihypertensive medication adherence (MA). Developing effective MA interventions requires identifying the most important factors influencing MA.

Objective

In this review, the authors aimed to meta-analyze the results of research testing associations between factors potentially influencing antihypertensive MA and assessed antihypertensive MA in historically underrepresented populations. Additional exploratory analyses focused on system-level factors, which have been understudied and may particularly impact disparities in MA.

Methods

A health sciences librarian assisted with searching across 10 databases. Inclusion criteria included (1) published in English, (2) sample of adults with hypertension, (3) ≥50% of participants having self-identified as a race/ethnicity underrepresented in the country where the study was conducted, and (4) reporting sufficient data to calculate effect size(s).

Results

Fifty-eight studies were eligible for inclusion. Nine factors met criteria for planned analyses. Older age (r = 0.08, P < .01; k = 26 studies) and higher income (r = 0.11, P = .01; k = 15) were significantly correlated with better MA. Having depressive symptoms was significantly correlated with worse MA (r = −0.18, P < .01; k = 11). Effect sizes for sex, education level, marital status, number of medications, comorbidities, and perceived social support were not significant. System-level factors examined included insurance coverage, access to healthcare, perceived barriers, having a primary care provider, perceptions of their healthcare provider, and experiences of discrimination in healthcare.

Conclusions

Understanding the impact of factors associated with antihypertensive MA in historically underrepresented adults can support development of targeted, culturally relevant MA interventions. Future research should examine the impact of system-level factors on antihypertensive MA among historically underrepresented populations.
Sexual Violence and Social Media Discourse
Authors: Glover Hilary Ashton , Hitt Amanda , Davenport Nikki , Casson Victoria , Blasingame Tabitha
Published: January 2024

Background

Sexual violence is prevalent on college campuses, yet formal disclosure and open dialogue are often muffled. Social media has become a powerful platform for survivors and presents an opportunity for researchers to explore social discourse surrounding sexual violence on campuses. Healthcare providers must be knowledgeable of campus climate surrounding sexual violence to provide patient-centered, trauma-informed care and mitigate the detrimental, long-term effects experienced by survivors.

Methods

Twitter, a social media and networking platform, was used to explore online discourse regarding sexual violence among college students. A conventional qualitative content analysis was implemented using two coders to explore data before identifying themes.

Results

The researchers identified 175 tweets that met the inclusion criteria. Three subthemes emerged: (a) lack of support, (b) powerlessness, and (c) victim blaming and shaming, which built the foundation for the overarching theme of rape culture.

Conclusion

Social media posts provide insight into survivor experiences and offer forensic nurses and healthcare providers the opportunity to discover information that survivors might not otherwise disclose. Forensic nurses should consider implementing innovative approaches to engage campus survivors and increase access to postassault care.
Cardiac sarcoidosis in a patient with ulcerative colitis: A case report and literature review
Authors: Moriichi Kentaro , Kashima Shin , Kobayashi Yu , Sugiyama Yuya , Murakami Yuki , Sasaki Takahiro , Kunogi Takehito , Takahashi Keitaro , Ando Katsuyoshi , Ueno Nobuhiro , Tanabe Hiroki , Date Ayumi , Yuzawa Sayaka , Fujiya Mikihiro
Published: January 2024

Rationale:

Both ulcerative colitis (UC) and sarcoidosis are chronic inflammatory diseases with unknown etiologies and are rare. However, the odds ratio in UC patients has been reported to range from 1.7 to 2.1, suggesting a potential etiology between sarcoidosis and UC. Furthermore, the underlying etiologies of UC and sarcoidosis remain unidentified. Sharing the experience of a UC patient with cardiac sarcoidosis could provide valuable insights to prevent sudden death in UC patients.

Patient concerns:

A 71-year-old Japanese woman was diagnosed with UC at 58-year-old and maintained remission on mesalazine treatment. She complained of just palpitation; therefore, she consulted a cardiologist.

Diagnoses:

The patient received a diagnosis of cardiac sarcoidosis with complicating ulcerative colitis based on the results of N-terminal prohormone of the brain natriuretic peptide (NT-proBNP), imaging examinations, and histology.

Intervention:

The patient was treated with prednisolone and methotrexate. The prednisolone was then tapered, and the methotrexate dose was adjusted based on her symptoms, imaging results, and laboratory findings.

Outcome:

She no longer had any symptoms, and the abnormal FDG uptake had disappeared after 2 years.

Lesson:

In UC patients, periodic or additional (in case of symptomatic) electrocardiography and NT-proBNP are recommended for the early detection of cardiac sarcoidosis, a life-threatening complication.
Lhermitte-Duclos disease with excessive calcification in a septuagenarian: A case report
Authors: Su Yang , Richard Seidu A. , Lan Zhigang , Zhang Yuekang
Published: January 2024

Rationale:

Lhermitte-Duclos disease (LDD), or dysplastic cerebellar gangliocytoma (DCG), is a rare tumor originating from the cerebellar cortex. LDD is a benign neuroglial tumor with uncertain prognosis. Over 200 cases have been reported in the literature mostly in the form of case reports. Thus, we present a spectacular case of LDD with excessive calcification in a female septuagenarian.

Patient concerns:

A 72-year-old female presented with progressive dizziness for 8 months and suffered a head and sacrococcygeal region injury 20 days prior to her admission in our neurosurgery department.

Diagnosis:

Computed tomography scan showed a right nonspecific cerebellar mass with striated calcification. Magnetic resonance imaging revealed a right “tiger-striped” alteration of the cerebellar cortex. H&E staining revealed a low grade glial neural tumor which was consistent with the diagnosis of LDD or DCG.

Intervention:

The lesion was total resected.

Outcomes:

The patient recovered well and the cerebellar dysfunctional symptoms subsided 3 months after the operation and 2 years follow-up revealed no recurrence of the lesion and no neurological deficits.

Lesion:

We postulate that the calcification of LDD is age-related and the pathogenesis of disease often observed in young adulthood.
Adjuvant trastuzumab for triple-positive breast cancer with chronic renal failure: A case report and review of literature
Authors: En Wen , Long Yuming
Published: January 2024

Rationale:

Although the occurrence of combined renal insufficiency among patients with breast cancer is even rarer, it poses a significant challenge in the treatment of these patients. Treating such patients often requires both targeted and endocrine therapies. However, oncologists lack evidence-based guidelines for managing renal function in patients with renal insufficiency.

Patients concern:

A 56-year-old menopausal female with a history of renal failure was diagnosed with triple-positive breast cancer and administered endocrine therapy and targeted therapy associated with hemodialysis after surgery.

Outcomes:

Under the premise of regular dialysis, the patient successfully completed endocrine therapy and targeted therapy for 1 year.

Discussion:

Patients with advanced triple-positive breast cancer, including those undergoing hemodialysis, require a combination of anti-human epidermal growth factor receptor-2 and endocrine therapies, The side effects of these 2 treatment methods are worth considering in patients with renal insufficiency.

Conclusion:

We report a case of triple-positive breast cancer in a patient undergoing hemodialysis. There was no difference in the treatment approach between patients with and without normal renal function.
Effectiveness of acupuncture combined with artificial tears in managing dry eye syndrome: A systematic review and meta-analysis
Authors: Wang Ying , Peng Jun , Xiao Li , Deng Ying , Lu Jing , Zhou Ya-Sha , Yang Yi-Jing , Peng Qing-Hua
Published: January 2024

Background:

Dry eye syndrome is an ocular surface disease with high incidence. Acupuncture combined with artificial tears is effective for treating dry eye syndrome. This study aimed to evaluate the evidence for the efficacy of acupuncture combined with artificial tears in dry eye syndrome by conducting a systematic review and meta-analysis.

Methods:

A systematic online search was performed from the date of database establishment to July 1, 2023. The study groups that addressed acupuncture combined with artificial tears for patients with dry eye syndrome (DES) and the control groups that addressed artificial tears were analyzed. The main outcomes were tear breakup time (BUT) and Schirmer I test (SIT), assessed as previously described.

Results:

Sixteen randomized or controlled trials met the selection criteria, and 1383 patients with DES were included in this study. The analysis results showed that BUT [Standard mean difference (SMD) = 1.25, 95% confidence interval (CI) (1.14, 1.37), P < .0001], SIT [SMD = 1.55, 95% CI (1.08, 2.02), P < .0001], and corneal fluorescein staining [SMD = –2.08, 95% CI (–2.96, –1.20), P < .00001] significantly improved in the trial groups compared with the control groups. The acupuncture treatment was more effective in reducing the levels of IL-6 (P < .0001) and TNF-α (P < .00001). The overall efficacy rate was better in the trial group than in the control group [odds ratio = 4.09, 95% CI (3.04, 5.51), P < .00001]. However, no significant difference was observed in the ocular surface disease index (P = .15) between the trial and control groups.

Conclusion:

The results of this study indicated that acupuncture combined with artificial tears could be considered safe, effective to patients with DES.
Bibliometric analysis of lupus nephritis in children from 1999 to 2022: A review
Authors: Ma Yunhong , Wang Shuangyi , Luo Fei , Zhang Yuan , Diao Juanjuan
Published: January 2024

Lupus nephritis (LN) is a complication of systemic lupus erythematosus and a damaging disease of the kidney. The injury of LN in children is more serious than that in adults. However, the literature in this field is numerous and complex, which brings great challenges for researchers to extract information. The purpose of this study is to carry out bibliometric analysis and visualization of published literatures, and identify current research hotspots and future research trends in this field. Literature was retrieved from the Web Of Science database from 1999 to 2022. The literature was analyzed and visualized using Citespace 6.1.R6, VOSviewer 1.6.18, and Microsoft Excel 2019. A total of 1059 articles were included in this study. In the past 13 years, an increase in the number of publications every year. Brunner HI is the author with the highest number of published and cited papers in this field, followed by Wenderfer SE. The United States and China are the countries with the highest number of published papers. University Toronto is the most productive institution, followed by University Cincinnati. The most prolific journal was Pediatric nephrology (IF 2.67), followed by lupus (IF 2.21). Lupus was cited the most, followed by Pediatric nephrology. The keyword burst showed the earliest and longest burst was antiphospholipid antibody, validation/risk/rituximab/safety is the current research hotspot. The article with the highest number of citations was Hochberg MC 1997 published in Arthritis Rheum. This study provides valuable information summary for the field of LN in children, which is helpful to strengthen the cooperation among countries, institutions and authors, and promote the research in the field of LN in children.
Treatment of gouty arthritis with traditional Chinese medicine decoction: Meta-analysis, network pharmacology analysis, and molecular docking
Authors: Qu Pengda , Du Shiyu , Wang Wei , Peng Zhaorong , Hu Qian , Wang Haiyang , Tang Xiaohu
Published: January 2024

Background:

Previous studies have shown that traditional Chinese medicine decoction (TCMD) could ameliorate the clinical symptoms and laboratory indicators of gouty arthritis (GA) patients. However, few investigations have been conducted on the efficacy and safety of TCMD for GA, the underlying mechanism of TCMD for GA, and the relationship between the TCMD active ingredients and GA targets.

Methods:

Randomized controlled trials of TCMD for GA were retrieved from Chinese and English databases. Meta-analysis was conducted by Stata 17 software. Potential sources of heterogeneity were identified through subgroup analysis, meta-regression, and heterogeneity test. Publication bias was assessed by Egger’s test and funnel plots. The ingredients and targets related to TCMD and GA were obtained from multiple databases, such as TCMSP and DrugBank. The protein-protein interaction network, GO and KEGG analysis was constructed using STRING and DAVID. Molecular docking and visualization of the results were completed by AutoDock and PyMOL software.

Results:

Eighty-four studies were included, involving 7151 patients and 10 outcome indicators. Meta-analysis showed that, compared to routine treatment, TCMD could better reduce the incidence of adverse events and the level of laboratory indicators including blood uric acid (BUA), C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), interleukin 6 (IL-6), interleukin 8 (IL-8), interleukin 1β (IL-1β), and tumor necrosis factor-α (TNF-α). In the section of network pharmacology, we retrieved 150 active ingredients and 303 target genes from the top 10 herbs in 84 studies, as well as 3082 disease targets and 195 cross targets of the herbs and GA. The top ranked ingredients, intersection targets, and signaling pathways included quercetin, kaempferol, and wogonin; AKT1, TNF, and TP53; as well as IL-17, HIF-1, and PI3K-AKT, etc. Among the 81 molecular docking results, we visualized 10 results with low binding energy, including IL1B and beta-sitosterol, MYC and beta-sitosterol, etc.

Conclusion:

TCMD could be a satisfactory complementary and alternative therapy for GA. However, it should be verified by further studies. Future research could be conducted from the following active ingredients, targets, and signal pathways, such as wogonin, sitosterol, and sitosterol; AKT1, TNF, IL6, and TP53; and IL-17, HIF-1, and PI3K-AKT signaling pathway.
Impact of evidence-based nursing on postoperative psychological state, quality of life, and function of affected limbs in breast cancer patients: An observational study
Authors: Wang Shaoman , He Peijuan , Liu Qin , Mao Juanjuan , Shen Songna
Published: January 2024

To analyze the effect of evidence-based nursing on postoperative psychological state, quality of life, and function of affected limbs in breast cancer (BC) patients. This study is a retrospective analysis. The clinical data of 122 BC patients in our hospital were selected and divided into evidence-based group and routine group according to different nursing programs. Patients in evidence-based group received evidence-based nursing, and patients in the conventional group received routine nursing intervention. The acceptance level of BC diagnosis in evidence-based group was significantly higher than that in the conventional group, showing statistical significance (P < .05). After intervention, Self-rating Anxiety Scale and Self-rating Depression Scale scores of both groups were significantly reduced, and the Self-rating Anxiety Scale and Self-rating Depression Scale scores in evidence-based group were significantly lower than those in conventional group, showing statistically significant difference (P < .05); Self-Esteem Scale scores were significantly increased in both groups after intervention, and the scores in evidence-based group were significantly higher than those in conventional group, showing statistically significant difference (P < .05). After intervention, in evidence-based group, the proportion of patients without edema was significantly increased, while the proportion of patients with mild, moderate and severe edema was significantly decreased, exhibiting statistically significant difference (P < .05). After intervention, the circumference difference of the healthy side and the affected side decreased significantly, which was much lower in evidence-based group, showing statistically significant difference (P < .05). After intervention, range of motion of the upper limbs increased significantly between the 2 groups, which was much higher in evidence-based group, exhibiting statistical significance (P < .05). The scores of quality of life (role, emotion, body, cognition and society dimension) in evidence-based group were higher than those in conventional group, exhibiting statistically significant difference (P < .05). Evidence-based nursing can develop more targeted nursing measures according to patients’ problems, thus effectively promoting the recovery of upper limb function of BC patients after surgery.