bluuebunny/crossref_metadata_2025 huggingface dataset:
Immune checkpoint inhibitors associated granulomatous small vessel vasculitis accompanied with tubulointerstitial nephritis: a case report
Authors: Tominaga Kenta , Takeuchi Kazuhiro , Takakuma Shoichiro , Sakamoto Emi , Hatanaka Saeko , Kajimoto Yusuke , Toda Etsuko , Terasaki Yasuhiro , Kunugi Shinobu , Terasaki Mika , Shimizu Akira
Published: March 2023

Background

Immune checkpoint inhibitors (ICIs) have provided significant benefits in cancer treatment, but they could develop immune-related adverse events (irAE). ICI-associated renal adverse effects are rare and tubulointerstitial nephritis (TIN) is the most common in the renal irAE. However, only a few case reports of renal vasculitis associated with ICI have been reported. In addition, the characteristics of infiltrating inflammatory cells of ICI-associated TIN and renal vasculitis have been uncertain.

Case presentation

A 65-year-old man received immune checkpoint inhibitors (ICIs), anti-CTLA-4 (cytotoxic T-lymphocyte-associated protein 4) and anti-PD-1 (programmed cell death 1) antibodies for aggravated metastatic malignant melanoma. About 1 week after the second administration of nivolumab and ipilimumab, acute kidney injury developed. A renal biopsy was performed that showed TIN and non-necrotizing granulomatous vasculitis in interlobular arteries. Massive CD3+ T cells and CD163+ macrophages infiltrated both tubulointerstitium and interlobular arteries. Many infiltrating cells tested positive for Ki-67 and PD-1 ligand (PD-L1), but negative for PD-1. In CD3+ T cells, CD8+ T cells were predominantly infiltrated, and these cells were positive for Granzyme B (GrB) and cytotoxic granule TIA-1, but negative for CD25, indicating antigen-independent activated CD8+ T cells. Infiltration of CD4+ T cells was noted without obvious CD4+ CD25+ regulatory T (Treg) cells. His renal dysfunction recovered within 2 months of treatment with prednisolone in addition to discontinuation of nivolumab and ipilimumab.

Conclusions

We herein reported a case of ICI-related TIN and renal granulomatous vasculitis with infiltration of massive antigen-independent activated CD8+ T cells and CD163+ macrophages, and none or few CD4+ CD25+ Treg cells. These infiltrating cells might be a characteristic of the development of renal irAE.
Controlling Nutritional Status (CONUT) score is a prognostic marker in III-IV NSCLC patients receiving first-line chemotherapy
Authors: Zhang Yi , Kong Fei-Fei , Zhu Zheng-Qiu , Shan Hai-Xia
Published: March 2023

Background

To investigate the prognostic impact of the controlling nutritional status (CONUT) score in non-small-cell lung cancer (NSCLC) patients receiving first-line chemotherapy.

Methods

We retrospectively reviewed 278 consecutive patients undergoing chemotherapy for stage III-IV NSCLC between May 2012 and July 2020. CONUT score was calculated by incorporating serum albumin, total cholesterol, and total lymphocyte count. The patients were divided into two groups: CONUT ≥ 3 and CONUT < 3, according to receiver operating characteristic (ROC) analysis. The associations of CONUT with clinicopathological factors and survival were evaluated.

Results

A high CONUT score was significantly associated with older age(P = 0.003), worse ECOG-PS(P = 0.018), advanced clinical stage(P = 0.006), higher systematic inflammation index (SII) (P < 0.001)and lower prognostic nutritional index (PNI) (P < 0.001).The high CONUT group had a significantly shorter progression-free survival(PFS) and overall survival(OS) than the low CONUT group. In the univariate analysis, higher SII, higher CONUT, advanced clinical stage and lower PNI were associated with worse PFS (Pall < 0.05). Worse ECOG-PS, higher SII, higher CONUT, advanced clinical stage and lower PNI were associated with worse OS (Pall < 0.05). In multivariate analysis, CONUT(HR, 2.487; 95%CI 1.818 ~ 3.403; P < 0.001) was independently associated with PFS, while PNI(HR, 0.676; 95%CI 0.494 ~ 0.927; P = 0.015) and CONUT(HR, 2.186; 95%CI 1.591 ~ 3.002; P < 0.001)were independently associated with OS. In ROC analysis, CONUT had a higher area under the ROC curve (AUC) for the prediction of 24-month PFS and OS than the SII or PNI. When the time-dependent AUC curve was used to predict PFS and OS, CONUT tended to maintain its predictive accuracy for long-term prognosis at a significantly higher level for an extended period after chemotherapy when compared with the other markers tested. The CONUT score showed better accuracy of predicting OS (C-index: 0.711) and PFS(C-index: 0.753).

Conclusion

CONUT score is an independent prognostic indicator of poor outcomes for patients with stage III-IV NSCLC and is superior to the SII and PNI in terms of prognostic ability.
IgG4-related ophthalmic disease masquerading as ciliary body tumors and scleritis in both eyes: a case report
Authors: Ma Jiayue , Xie Manyun , Long Kejun , Deng Mi , Zhou Liang , Luo Jing
Published: March 2023

Background

To report a rare case of IgG4-related ophthalmic disease (IgG4-ROD) manifesting as intraocular masses and scleritis in both eyes in a 61-year-old male and to investigate the changes in multimodal imaging features of the lesion sites and helper T-cell type 1 (Th 1)/Th 2/Th 17 cytokine levels in the aqueous humor.

Case presentation

A patient with IgG4-ROD seemingly manifested with an intraocular tumor in the left eye and sequentially, with an inflammatory mass in the ciliary body and scleritis in the right eye. The patient complained of vision loss of 6 months duration in the left eye at his first visit. With a preliminary diagnosis of an intraocular tumor, enucleation of the left eyeball and histopathological examination were performed. Approximately 3 months later, the patient started to experience headache, eye pain, and declining vision in the right eye. Ophthalmic imaging revealed a ciliary mass and scleritis. Th 1/Th 2/Th 17 cytokine levels and multimodal imaging findings were analyzed before and after corticosteroid treatment. Histopathological examination and immunohistochemistry (IHC) of the enucleated left eye demonstrated lymphoplasmacytic infiltration with an IgG4+/IgG+ cell ratio of approximately 40%, pointing to the diagnosis of probable IgG4-ROD. Long-term treatment with corticosteroids led to significant improvement in the signs and symptoms of the left eye. Th 1/Th 2/Th 17 cytokine profile monitoring of the aqueous humor and multimodal imaging of the right eye showed gradual regression of the mass and attenuation of ocular inflammation during treatment.

Conclusions

Patients with an atypical presentation of IgG4-ROD, such as intraocular masses and scleritis, are likely to experience a significant delay in diagnosis. This case demonstrates the significance of IgG4-ROD in the differential diagnosis of intraocular tumors and ocular inflammation. IgG4-RD is a newly diagnosed disease with multi-organ involvement and little is known about its pathogenesis, particularly in the eye. The present case will open new challenges in the clinico-pathological diagnosis and research of this disease. Combined investigations of multimodal imaging and cytokine level detection of intraocular fluid provide a new and effective way to monitor disease progression.
Weight-dependent and weight-independent effects of dulaglutide on blood pressure in patients with type 2 diabetes
Authors: Ferdinand Keith C. , Dunn Julia , Nicolay Claudia , Sam Flora , Blue Emily K. , Wang Hui
Published: March 2023

Background

Patients with type 2 diabetes (T2D) treated with glucagon-like peptide-1 receptor agonists may experience reductions in weight and blood pressure. The primary objective of the current study was to determine the weight-dependent and weight-independent effects of ~ 6 months treatment with dulaglutide 1.5 mg treatment in participants with T2D.

Methods

Mediation analysis was conducted for five randomized, placebo-controlled trials of dulaglutide 1.5 mg to estimate the weight-dependent (i.e., mediated by weight) and weight-independent effects from dulaglutide vs. placebo on change from baseline for systolic blood pressure (SBP), diastolic blood pressure (DBP), and pulse pressure. A random-effects meta-analysis combined these results. To investigate a dose response between dulaglutide 4.5 mg and placebo, mediation analysis was first conducted in AWARD-11 to estimate the weight-dependent and weight-independent effects of dulaglutide 4.5 mg vs. 1.5 mg, followed by an indirect comparison with the mediation result for dulaglutide 1.5 mg vs. placebo.

Results

Baseline characteristics were largely similar across the trials. In the mediation meta-analysis of placebo-controlled trials, the total treatment effect of dulaglutide 1.5 mg after placebo-adjustment on SBP was − 2.6 mmHg (95% CI − 3.8, − 1.5; p < 0.001) and was attributed to both a weight-dependent effect (− 0.9 mmHg; 95% CI: − 1.4, − 0.5; p < 0.001) and a weight-independent effect (− 1.5 mmHg; 95% CI: − 2.6, − 0.3; p = 0.01), accounting for 36% and 64% of the total effect, respectively. For pulse pressure, the total treatment effect of dulaglutide (− 2.5 mmHg; 95% CI: − 3.5, − 1.5; p < 0.001) was 14% weight-dependent and 86% weight-independent. For DBP there was limited impact of dulaglutide treatment, with only a small weight-mediated effect. Dulaglutide 4.5 mg demonstrated an effect on reduction in SBP and pulse pressure beyond that of dulaglutide 1.5 mg which was primarily weight mediated.

Conclusions

Dulaglutide 1.5 mg reduced SBP and pulse pressure in people with T2D across the placebo-controlled trials in the AWARD program. While up to one third of the effect of dulaglutide 1.5 mg on SBP and pulse pressure was due to weight reduction, the majority was independent of weight. A greater understanding of the pleotropic effects of GLP-1 RA that contribute to reduction in blood pressure could support developing future approaches for treating hypertension.

Trial registrations (clinicaltrials.gov) NCT01064687, NCT00734474, NCT01769378, NCT02597049, NCT01149421, NCT03495102
The vascular function effects of adding exenatide or meal insulin to basal insulin therapy in early type 2 diabetes
Authors: Retnakaran Ravi , Pu Jiajie , Ye Chang , Emery Alexandra , Kramer Caroline K. , Zinman Bernard
Published: March 2023

Objective

Basal insulin glargine has a neutral effect on cardiovascular risk in type 2 diabetes (T2DM). In practice, basal insulin is often paired with a glucagon-like peptide-1 receptor agonist (GLP1-RA) or meal insulin; however, the cardiovascular implications of these combinations have not been fully elucidated. In this context, we sought to evaluate the vascular function effects of adding the GLP1-RA exenatide or meal insulin lispro to basal glargine therapy in early T2DM.

Methods

In this 20-week trial, adults with T2DM of < 7-years duration were randomized to 8-weeks treatment with (i) insulin glargine (Glar), (ii) glargine + thrice-daily lispro (Glar/Lispro), or (iii) glargine + twice-daily exenatide (Glar/Exenatide), followed by 12-weeks washout. At baseline, 8-weeks, and washout, fasting endothelial function was assessed with reactive hyperemia index (RHI) measurement by peripheral arterial tonometry.

Results

At baseline, there were no differences in blood pressure (BP), heart rate (HR) or RHI between participants randomized to Glar (n = 24), Glar/Lispro (n = 24), and Glar/Exenatide (n = 25). At 8-weeks, Glar/Exenatide decreased systolic BP (mean − 8.1 mmHg [95%CI − 13.9 to − 2.4], p = 0.008) and diastolic BP (mean − 5.1 mmHg [− 9.0 to − 1.3], p = 0.012) compared to baseline, with no significant changes in HR or RHI. Notably, baseline-adjusted RHI (mean ± SE) did not differ between the groups at 8-weeks (Glar 2.07 ± 0.10; Glar/Lispro 2.00 ± 0.10; Glar/Exenatide 1.81 ± 0.10; p = 0.19), nor did baseline-adjusted BP or HR. There were no differences between the groups in baseline-adjusted RHI, BP or HR after 12-weeks washout.

Conclusion

Adding either exenatide or lispro to basal insulin therapy does not appear to affect fasting endothelial function in early T2DM.

Trial Registration: ClinicalTrials.Gov NCT02194595.
RNA N6-methyladenosine modification in female reproductive biology and pathophysiology
Authors: Huang Erqing , Chen Lijuan
Published: March 2023

Gene expression and posttranscriptional regulation can be strongly influenced by epigenetic modifications. N6-methyladenosine, the most extensive RNA modification, has been revealed to participate in many human diseases. Recently, the role of RNA epigenetic modifications in the pathophysiological mechanism of female reproductive diseases has been intensively studied. RNA m6A modification is involved in oogenesis, embryonic growth, and foetal development, as well as preeclampsia, miscarriage, endometriosis and adenomyosis, polycystic ovary syndrome, premature ovarian failure, and common gynaecological tumours such as cervical cancer, endometrial cancer, and ovarian cancer. In this review, we provide a summary of the research results of m6A on the female reproductive biology and pathophysiology in recent years and aim to discuss future research directions and clinical applications of m6A-related targets. Hopefully, this review will add to our understanding of the cellular mechanisms, diagnostic biomarkers, and underlying therapeutic strategies of female reproductive system diseases.
Sex-specific innate immunity and ageing in long-lived fresh water turtles (Kinosternon flavescens: Kinosternidae)
Authors: Bronikowski Anne M. , Hedrick Ashley R. , Kutz Greta A. , Holden Kaitlyn G. , Reinke Beth , Iverson John B.
Published: March 2023

Background

The progressive deregulation of the immune system with age, termed immunosenescence, has been well studied in mammalian systems, but studies of immune function in long-lived, wild, non-mammalian populations are scarce. In this study we leverage a 38-year mark-recapture study to quantify the relationships among age, sex, survival, reproductive output and the innate immune system in a long-lived reptile, yellow mud turtles (Kinosternon flavescens; Testudines; Kinosternidae).

Methods

We estimated rates of survival and age-specific mortality by sex based on mark-recapture data for 1530 adult females and 860 adult males over 38 years of captures. We analyzed bactericidal competence (BC), and two immune responses to foreign red blood cells - natural antibody-mediated haemagglutination (NAbs), and complement-mediated haemolysis ability (Lys) - in 200 adults (102 females; 98 males) that ranged from 7 to 58 years of age captured in May 2018 during their emergence from brumation, and for which reproductive output and long-term mark-recapture data were available.

Results

We found that females are smaller and live longer than males in this population, but the rate of accelerating mortality across adulthood is the same for both sexes. In contrast, males exhibited higher innate immunity than females for all three immune variables we measured. All immune responses also varied inversely with age, indicating immunosenescence. For females that reproduced in the preceding reproductive season, egg mass (and therefore total clutch mass) increased with age,. In addition to immunosenescence of bactericidal competence, females that produced smaller clutches also had lower bactericidal competence.

Conclusions

Contrary to the general vertebrate pattern of lower immune responses in males than females (possibly reflecting the suppressive effects of androgens), we found higher levels of all three immune variables in males. In addition, contrary to previous work that found no evidence of immunosenescence in painted turtles or red-eared slider turtles, we found a decrease in bactericidal competence, lysis ability, and natural antibodies with age in yellow mud turtles.
A mobilization poster stimulates early in-hospital rehabilitation after cardiac surgery: a prospective sequential-group study
Authors: Halfwerk Frank R. , Wielens Nicole , Hulskotte Stephanie , Brusse-Keizer Marjolein , Grandjean Jan G.
Published: March 2023

Background

Patients infrequently mobilize at the surgical ward after cardiac surgery. Inactivity results in prolonged hospital stay, readmissions and increased cardiovascular mortality. Next, the course of in-hospital mobilization activities for patients is unclear. The aim was to evaluate early mobilization after heart surgery with a mobilization poster on the Activity Classification Guide for Inpatient Activities score from the American College for Sports Medicine (ACSM). Second, to develop a Thorax Centrum Twente (TCT) score to assess distinctive activities performed.

Methods

A poster was developed for the Moving is Improving! study to stimulate hospital mobilization after heart surgery. In this sequential-group study at a cardiothoracic surgery ward, 32 patients were included in the usual care group and 209 patients in the poster mobilization group. Change of ACSM and TCT scores over time were both defined as primary endpoints. Secondary endpoints included length of stay and survival. A subgroup analysis for coronary artery bypass grafting (CABG) was performed.

Results

ACSM score increased during hospital stay (p < 0.001). No significant increase of ACSM score was observed with a mobilization poster (p = 0.27), nor in the CABG subgroup (p = 0.15). The poster increased mobility to chair, toilet, corridor (all p < 0.01) and cycle ergometer (p = 0.02) as measured by the activity-specific TCT scores, without differences in length of stay or survival.

Conclusions

ACSM score measured day-to-day functional changes, without significant differences between the poster mobilization and usual care group. Actual activities measured with the TCT score did improve. The mobilization poster is now new standard care, and effects in other centers and other departments should be assessed.

Trial registration

This study does not fall under the ICMJE trial definition and was not registered.
Extensive sequence duplication in Arabidopsis revealed by pseudo-heterozygosity
Authors: Jaegle Benjamin , Pisupati Rahul , Soto-Jiménez Luz Mayela , Burns Robin , Rabanal Fernando A. , Nordborg Magnus
Published: March 2023

Background

It is apparent that genomes harbor much structural variation that is largely undetected for technical reasons. Such variation can cause artifacts when short-read sequencing data are mapped to a reference genome. Spurious SNPs may result from mapping of reads to unrecognized duplicated regions. Calling SNP using the raw reads of the 1001 Arabidopsis Genomes Project we identified 3.3 million (44%) heterozygous SNPs. Given that Arabidopsis thaliana (A. thaliana) is highly selfing, and that extensively heterozygous individuals have been removed, we hypothesize that these SNPs reflected cryptic copy number variation.

Results

The heterozygosity we observe consists of particular SNPs being heterozygous across individuals in a manner that strongly suggests it reflects shared segregating duplications rather than random tracts of residual heterozygosity due to occasional outcrossing. Focusing on such pseudo-heterozygosity in annotated genes, we use genome-wide association to map the position of the duplicates. We identify 2500 putatively duplicated genes and validate them using de novo genome assemblies from six lines. Specific examples included an annotated gene and nearby transposon that transpose together. We also demonstrate that cryptic structural variation produces highly inaccurate estimates of DNA methylation polymorphism.

Conclusions

Our study confirms that most heterozygous SNP calls in A. thaliana are artifacts and suggest that great caution is needed when analyzing SNP data from short-read sequencing. The finding that 10% of annotated genes exhibit copy-number variation, and the realization that neither gene- nor transposon-annotation necessarily tells us what is actually mobile in the genome suggests that future analyses based on independently assembled genomes will be very informative.
A novel rhein-huprine hybrid ameliorates disease-modifying properties in preclinical mice model of Alzheimer’s disease exacerbated with high fat diet
Authors: Espinosa-Jiménez Triana , Cano Amanda , Sánchez-López Elena , Olloquequi Jordi , Folch Jaume , Bulló Mònica , Verdaguer Ester , Auladell Carme , Pont Caterina , Muñoz-Torrero Diego , Parcerisas Antoni , Camins Antoni , Ettcheto Miren
Published: March 2023

Background

Alzheimer’s disease (AD) is characterized by a polyetiological origin. Despite the global burden of AD and the advances made in AD drug research and development, the cure of the disease remains elusive, since any developed drug has demonstrated effectiveness to cure AD. Strikingly, an increasing number of studies indicate a linkage between AD and type 2 diabetes mellitus (T2DM), as both diseases share some common pathophysiological features. In fact, β-secretase (BACE1) and acetylcholinesterase (AChE), two enzymes involved in both conditions, have been considered promising targets for both pathologies. In this regard, due to the multifactorial origin of these diseases, current research efforts are focusing on the development of multi-target drugs as a very promising option to derive effective treatments for both conditions.

In the present study, we evaluated the effect of rhein-huprine hybrid (RHE-HUP), a synthesized BACE1 and AChE inhibitor, both considered key factors not only in AD but also in metabolic pathologies. Thus, the aim of this study is to evaluate the effects of this compound in APP/PS1 female mice, a well-established familial AD mouse model, challenged by high-fat diet (HFD) consumption to concomitantly simulate a T2DM-like condition.

Results

Intraperitoneal treatment with RHE-HUP in APP/PS1 mice for 4 weeks reduced the main hallmarks of AD, including Tau hyperphosphorylation, Aβ42 peptide levels and plaque formation. Moreover, we found a decreased inflammatory response together with an increase in different synaptic proteins, such as drebrin 1 (DBN1) or synaptophysin, and in neurotrophic factors, especially in BDNF levels, correlated with a recovery in the number of dendritic spines, which resulted in memory improvement. Notably, the improvement observed in this model can be attributed directly to a protein regulation at central level, since no peripheral modification of those alterations induced by HFD consumption was observed.

Conclusions

Our results suggest that RHE-HUP could be a new candidate for the treatment of AD, even for individuals with high risk due to peripheral metabolic disturbances, given its multi-target profile which allows for the improvement of some of the most important hallmarks of the disease.
Critically ill severe hypothyroidism: a retrospective multicenter cohort study
Authors: Bourcier Simon , Coutrot Maxime , Ferré Alexis , Van Grunderbeeck Nicolas , Charpentier Julien , Hraiech Sami , Azoulay Elie , Nseir Saad , Aissaoui Nadia , Messika Jonathan , Fillatre Pierre , Persichini Romain , Carreira Serge , Lautrette Alexandre , Delmas Clément , Terzi Nicolas , Mégarbane Bruno , Lascarrou Jean-Baptiste , Razazi Keyvan , Repessé Xavier , Pichereau Claire , Contou Damien , Frérou Aurélien , Barbier François , Ehrmann Stephan , de Montmollin Etienne , Sztrymf Benjamin , Morawiec Elise , Bigé Naïke , Reuter Danielle , Schnell David , Ellrodt Olivier , Dellamonica Jean , Combes Alain , Schmidt Matthieu
Published: March 2023

Background

Severe hypothyroidism (SH) is a rare but life-threatening endocrine emergency. Only a few data are available on its management and outcomes of the most severe forms requiring ICU admission. We aimed to describe the clinical manifestations, management, and in-ICU and 6-month survival rates of these patients.

Methods

We conducted a retrospective, multicenter study over 18 years in 32 French ICUs. The local medical records of patients from each participating ICU were screened using the International Classification of Disease 10th revision. Inclusion criteria were the presence of biological hypothyroidism associated with at least one cardinal sign among alteration of consciousness, hypothermia and circulatory failure, and at least one SH-related organ failure.

Results

Eighty-two patients were included in the study. Thyroiditis and thyroidectomy represented the main SH etiologies (29% and 19%, respectively), while hypothyroidism was unknown in 44 patients (54%) before ICU admission. The most frequent SH triggers were levothyroxine discontinuation (28%), sepsis (15%), and amiodarone-related hypothyroidism (11%). Clinical presentations included hypothermia (66%), hemodynamic failure (57%), and coma (52%). In-ICU and 6-month mortality rates were 26% and 39%, respectively. Multivariable analyses retained age > 70 years [odds ratio OR 6.01 (1.75–24.1)] Sequential Organ-Failure Assessment score cardiovascular component ≥ 2 [OR 11.1 (2.47–84.2)] and ventilation component ≥ 2 [OR 4.52 (1.27–18.6)] as being independently associated with in-ICU mortality.

Conclusions

SH is a rare life-threatening emergency with various clinical presentations. Hemodynamic and respiratory failures are strongly associated with worse outcomes. The very high mortality prompts early diagnosis and rapid levothyroxine administration with close cardiac and hemodynamic monitoring.
Territories in Transition: how social contexts influence wildland fire adaptive capacity in rural Northwestern European Mediterranean areas
Authors: Uyttewaal Kathleen , Prat-Guitart Núria , Ludwig Fulco , Kroeze Carolien , Langer E. R.
Published: March 2023

Background

Rural and semi-rural areas are complex and dynamic social-ecological systems, many of which have experienced profound impacts from wildland fires, particularly this decade. Under uncertain climate change conditions, these areas require new adaptive strategies to support landscape and community resilience. While these areas vary widely, some patterns of local social context have become apparent through wildland fire research. These patterns can help decision-makers better understand what influences communities’ abilities to adapt to fire. We focused our study on a northwestern European Mediterranean context, where communities are adapting to wildland fire and other climate change impacts through varied programs and policies. This area is composed of diverse landscapes, cultures, histories, languages and governance structures, but it also shares fire-based learning networks and collaborations, providing a sound indicator of shared elements of social context. Our study analyzed local social contexts in rural areas of Spain, Italy and France and assessed how these may inform adaptive capacity to wildland fire. A two-step process achieved this: (1) a targeted literature review of local social context elements as they relate to wildland fire in Mediterranean Europe; and (2) conducting semi-structured interviews with 20 key experts in rural Mediterranean areas, including fire managers, foresters, local administrators and technicians.

Results

Results illustrate numerous shared patterns in rural social contexts that influence local fire adaptive capacity. Dynamic local relationships among residents, local fire knowledge and environmental movements, the role of fire managers and administrators, and embeddedness in broader sociopolitical trends all interconnect to influence local fire adaptive capacity. Some key elements of context can act as primary enablers or barriers to this process, such as the presence (or lack) of local fire knowledge, and the opportunity (or lack thereof) for sustainable local economic development. Results also demonstrate high diversity in terms of governance structures and development trajectories.

Conclusions

We argue the need for deepened empirical transdisciplinary research to connect fire and land management tailored to local characteristics. Centering these local perspectives and diverse cultural values is necessary to foster long term adaptive wildland fire management strategies in rural Mediterranean communities and globally.
Remixing to Queer the Archives of Diaspora: Qajar Photography and the Persian Carpet
Authors: Akhtari Nazli
Published: March 2023

This article reveals how engagements with the photographic archives of premodern Iran and the Persian carpet break open transtemporal, affective, and queer interplays in diaspora. Examining a digital remix of a photograph of a Qajar princess, ‘Ismat al-Dowlah, from the archives of nineteenth-century Iran, the article argues that the digital (mis)use of archives exposes what forms such as the Persian carpet and photography erase: each medium's close ties with power, labor, gender, and sexuality. It develops a relational approach to understandings of photography that highlights the performative registers for a diasporic gaze while also troubling the imperial investment in understanding photography's history and its practices as a new technology that developed in the nineteenth century. This work considers how unlearning the history of Qajar photography entails deemphasizing the Qajar's king Naser Al Din Shah's fascination with photography's technological newness and instead exposes what desires his fascination was tethered to. This piece brings into conversation techno-historical overlaps between carpet weaving, the Jacquard machine, and computational arts, opening up critical questions about gender vis-à-vis production, labor, and computation within both carpets and computers as media interface.
Appropriate Feminisms: Ambivalence and Citational Practice in Appropriate Behavior
Authors: Bradbury-Rance Clara
Published: March 2023

Across her body of work in film, television, and digital media, Desiree Akhavan has captured the awkward politics of cultural production for female filmmakers and media-makers. Yet she has also refused to straightforwardly align her work with feminist critiques of dominant cultural production practices, however much she is interpellated by them. Akhavan, a queer woman of color in a racist, sexist, and homophobic industry, negotiates both contemporary feminism's potentials for solidarity and its intersectional shortcomings. Akhavan's autobiographical characters wrestle with the need for social justice while questioning the “appropriate behaviors” demanded by serious commitments to the cause. Her work reveals the ambivalence of feminist attachments. This article reads the queer feminist politics of Akhavan's work, with a particular focus on her debut feature Appropriate Behavior (UK/US, 2014), through the lens of citational practice. The author argues that Akhavan employs citational codes that function in Clare Hemmings's words as a “storytelling tactic,” sustaining normative narratives about feminism's recent past. By employing an ambivalent trope that the author calls citation→disavowal, Akhavan troubles both the dominant cultures she is excluded from and the viability and legibility of her place within the movements that resist them.
Understanding the Unique Challenges Faced by Homeless Patients With Acute Traumatic Neurosurgical Injuries
Authors: Cole Kyril L. , Findlay Matthew C. , Earl Emma , Sherrod Brandon A. , Cutler Christopher B. , Nguyen Sarah , Grandhi Ramesh , Menacho Sarah T.
Published: March 2023

BACKGROUND:

Homelessness is associated with high risk of acute neurotraumatic injury in the ∼600 000 Americans affected on any given night.

OBJECTIVE:

To compare care patterns and outcomes between homeless and nonhomeless individuals with acute neurotraumatic injuries.

METHODS:

Adults hospitalized for acute neurotraumatic injuries between January 1, 2015, and December 31, 2020, were identified in this retrospective cross-sectional study at our Level 1 trauma center. We evaluated demographics, in-hospital characteristics, discharge dispositions, readmissions, and adjusted readmission risk.

RESULTS:

Of 1308 patients, 8.5% (n = 111) were homeless on admission to neurointensive care. Compared with nonhomeless individuals, homeless patients were younger (P = .004), predominantly male (P = .003), and less frail (P = .003) but had similar presenting Glasgow Coma Scale scores (P = .85), neurointensive care unit stay time (P = .15), neurosurgical interventions (P = .27), and in-hospital mortality (P = .17). Nevertheless, homeless patients had longer hospital stays (11.8 vs 10.0 days, P = .02), more unplanned readmissions (15.3% vs 4.8%, P < .001), and more complications while hospitalized (54.1% vs 35.8%, P = .01), particularly myocardial infarctions (9.0% vs 1.3%, P < .001). Homeless patients were mainly discharged to their previous living situation (46.8%). Readmissions were primarily for acute-on-chronic intracranial hematomas (4.5%). Homelessness was an independent predictor of 30-day unplanned readmissions (odds ratio 2.41 [95% CI 1.33-4.38, P = .004]).

CONCLUSION:

Homeless individuals experience longer hospital stays, more inpatient complications such as myocardial infarction, and more unplanned readmissions after discharge compared with their housed counterparts. These findings combined with limited discharge options in the homeless population indicate that better guidance is needed to improve the postoperative disposition and long-term care of this vulnerable patient population.
Congenitally Fused Cervical Spine Is Associated With Adjacent-Level Degeneration in the Absence of Cervical Spine Surgery
Authors: Friedman Gabriel N. , Grannan Benjamin L. , Zinzuwadia Aniket , Williams Ziv M. , Coumans Jean-Valery
Published: March 2023

BACKGROUND:

Cervical fusion surgery is associated with adjacent-level degeneration, but surgical and technical factors are difficult to dissociate from the mechanical effects of the fusion itself.

OBJECTIVE:

To determine the effect of fusion on adjacent-level degeneration in unoperated patients using a cohort of patients with congenitally fused cervical vertebrae.

METHODS:

We identified 96 patients with incidental single-level cervical congenital fusion on computed tomography imaging. We compared these patients to an age-matched control cohort of 80 patients without congenital fusion. We quantified adjacent-level degeneration through direct measurements of intervertebral disk parameters as well as the validated Kellgren & Lawrence classification scale for cervical disk degeneration. Ordinal logistic regression and 2-way analysis of variance testing were performed to correlate extent of degeneration with the congenitally fused segment.

RESULTS:

Nine hundred fifty-five motion segments were analyzed. The numbers of patients with C2-3, C3-4, C4-5, C5-6, and C6-7 congenitally fused segments were 47, 11, 11, 17, and 9, respectively. We found that patients with congenital fusion at C4-C5 and C5-C6 had a significantly greater extent of degeneration at adjacent levels compared with the degree of degeneration at the same levels in control patients and in patients with congenital fusion at other cervical levels, even while controlling for expected degeneration and age.

CONCLUSION:

Taken together, our data suggest that congenitally fused cervical spinal segments at C4-C5 and C5-C6 are associated with adjacent-level degeneration independent of fixation instrumentation. This study design removes surgical factors that might contribute to adjacent-level degeneration.
Epidermal growth factor receptor signaling protects epithelia from morphogenetic instability and tissue damage in Drosophila
Authors: Yoshida Kentaro , Hayashi Shigeo
Published: March 2023

Dying cells in the epithelia communicate with neighboring cells to initiate coordinated cell removal to maintain epithelial integrity. Naturally occurring apoptotic cells are mostly extruded basally and engulfed by macrophages. Here, we have investigated the role of Epidermal growth factor (EGF) receptor (EGFR) signaling in the maintenance of epithelial homeostasis. In Drosophila embryos, epithelial tissues undergoing groove formation preferentially enhanced extracellular signal-regulated kinase (ERK) signaling. In EGFR mutant embryos at stage 11, sporadic apical cell extrusion in the head initiates a cascade of apical extrusions of apoptotic and non-apoptotic cells that sweeps the entire ventral body wall. Here, we show that this process is apoptosis dependent, and clustered apoptosis, groove formation, and wounding sensitize EGFR mutant epithelia to initiate massive tissue disintegration. We further show that tissue detachment from the vitelline membrane, which frequently occurs during morphogenetic processes, is a key trigger for the EGFR mutant phenotype. These findings indicate that, in addition to cell survival, EGFR plays a role in maintaining epithelial integrity, which is essential for protecting tissues from transient instability caused by morphogenetic movement and damage.
Πώς καταγράφηκε ο 20ός αιώνας στα ελληνικά σχολικά εγχειρίδια Ιστορίας από την χούντα (1967) μέχρι σήμερα (2022)
Authors: Σκυθιώτης Πέτρος
Published: March 2023

Η παρούσα διδακτορική διατριβή επικεντρώνεται στην διερεύνηση, καταγραφή και σύγκριση των ερμηνευτικών σχημάτων και ιδεολογικών κατευθύνσεων στις αφηγήσεις με τις οποίες τα ελληνικά σχολικά εγχειρίδια Ιστορίας από την χούντα (1967) μέχρι σήμερα (2022) κατέγραψαν στα περιεχόμενά τους την Ιστορία του 20ού αιώνα. Με ένα μεθοδολογικό μείγμα Ποιοτικής Ανάλυσης Περιεχομένου, Συγκριτικής Ανάλυσης και ιστορικο-κριτικής προσέγγισης αναλύονται και συγκρίνονται τα σχετικά περιεχόμενα 24 ελληνικών σχολικών εγχειριδίων Ιστορίας που χρησιμοποιήθηκαν σε Δημοτικό, Γυμνάσιο, Λύκειο και σε μαθήματα επιλογής την περίοδο 1967-2022, ώστε να εντοπιστούν και να καταγραφούν τα ερμηνευτικά σχήματα, οι ιδεολογικές κατευθύνσεις, οι εμφάσεις και οι αποσιωπήσεις των περιεχομένων· και έπειτα να καταγραφούν και να συγκριθούν οι μετασχηματισμοί τους ως μετασχηματισμοί του συνολικού ιστορικού αφηγήματος και ερμηνείας στον άξονα του χρόνου. Τα αποτελέσματα επιβεβαιώνουν την θεωρητική θέση της στενής συνάρτησης του ιδεολογικοπολιτικού ρόλου της σχολικής ιστορίας με το εκάστοτε κοινωνικοϊστορικό πλαίσιο. Αναδεικνύεται, έτσι, ο ρόλος του σχολικού εγχειριδίου ως Politicum και οι μετασχηματισμοί που λαμβάνει σε μορφή και περιεχόμενο: η ιστορικότητά του ως κοινωνικοπολιτισμικό προϊόν-αποτύπωμα μέσα από την θεσμική ιστορικοποίηση που εκφράζει ως διαμορφωτής-εργαλείο.
Reliability of the 44-question Home Fall Hazard Assessment Tool and personal characteristics associated with home hazards among the Thai elderly
Authors: Wittayapun Yuwadee , Nawarat Jiraphat , Lapmanee Sarawut , Mackenzie Lynette , Lektip Charupa
Published: March 2023

Background: The 44-question Thai Home Fall Hazard Assessment Tool (Thai-HFHAT) was developed to assist healthcare professionals in identifying the risk of falls among community-dwelling elderly from their home environment. However, the reliability of this tool has not been studied. This study aimed to examine the reliability of the 44-question Thai-HFHAT and determine the personal characteristics associated with home hazards.

Methods: A descriptive cross-sectional study design was used to evaluate interrater reliability. The participants in this study were 51 elderly people from various types of Thai houses: a one-story elevated house, a one-story non-elevated house, and a house with two or more floors, 51 caregivers of elderly patients, and 5 village health volunteers (VHV). A prospective design was used to evaluate test-retest reliability with older people at different times in their homes. All participants answered 44 Thai-HFHAT questions to determine inter-rater and test-retest reliabilities. The reliabilities were analyzed using an intra-class correlation coefficient (ICC). Personal characteristics including sex, occupation, and education were used to identify the factors affecting home hazards, and linear regression was used to analyze.

Results: The ICC of inter-rater reliability of the 44-question Thai-HFHAT was 0.74 (95% CI: 0.57-0.84) and the test-retest reliability was 0.80 (95% CI: 0.64-0.88) for the elderly, 0.80 (95% CI: 0.65-0.89) for the caregivers and 0.70 (95% CI: 0.477-0.83) for the VHV. Personal business career and education level grades 1-3 are less than 0.05, which showed these factors had a significant relationship with the 44-question Thai-HFHAT score as the dependent variable.

Conclusions: The 44-question Thai-HFHAT is suitable for home hazard assessment among the elderly in Thailand. Further studies are needed to investigate changes in the house environment after using the 44-question Thai-HFHAT to determine which changes can reduce fall risk.
The effect of Vitamin D levels on the course of COVID-19 in hospitalized patients – a 1-year prospective cohort study
Authors: Siuka Darko , Saletinger Rajko , Uršič Jure , Jevnikar Kristina , Janša Rado , Štubljar David , Osredkar Joško
Published: March 2023

Background: The aim of the current study was to assess the patients with COVID-19 and the impact of vitamin D supplementation on the course of COVID-19. 

Methods: This prospective cohort study included patients hospitalized due to COVID-19 between December 2020 and December 2021. Patients' demographic, clinical, and laboratory parameters were analysed.  

Results: 301 participants were enrolled in the study. 46 (15,3%) had moderate, and 162 (53,8%) had severe COVID-19. 14 (4,7%) patients died, and 30 (10,0%) were admitted to the ICU due to disease worsening. The majority needed oxygen therapy (n=224; 74,4%). Average vitamin 25(OH)D3 levels were below optimal at the admittance, and vitamin D deficiency was detected in 205 individuals. More male patients were suffering from vitamin D deficiency. Patients with the more severe disease showed lower levels of vitamin 25(OH)D3 in their blood. The most severe group of patients had more symptoms that lasted significantly longer with progressing disease severity. This group of patients also suffered from more deaths, ICU admissions, and treatments with dexamethasone, remdesivir, and oxygen. 

Conclusion: Patients with the severe course of COVID-19 were shown to have increased inflammatory parameters, increased mortality, and higher incidence of vitamin D deficiency. The results suggest that the vitamin D deficiency might represent a significant risk factor for a severe course of COVID-19.
History of political and legal doctrines
Authors: Kapicyn Vladimir , Akmalova Al'fiya , Arsanukaeva M.S. , Shirinyanc A.A.
Published: March 2023

The textbook examines the main political and legal doctrines, the study of which forms the general cultural and professional competencies necessary in research and teaching activities. Along with the traditional range of topics, attention is also paid to the analysis of controversial issues in the assessment of individual legal and political doctrines that may be the subject of consideration in the scientific work of undergraduates. The textbook is provided with electronic supplements, including methodological materials.
Meets the requirements of the federal state educational standards of higher education of the latest generation.
For undergraduates studying in the field of training 40.04.01 "Jurisprudence", as well as graduate students, students, anyone interested in the theory and history of jurisprudence.
Branch-Price-and-Cut-Based Solution of Order Batching Problems
Authors: Wahlen Julia , Gschwind Timo
Published: March 2023

Given a set of customer orders each comprising one or more individual items to be picked, the order batching problem (OBP) in warehousing consists of designing a set of picking batches such that each customer order is assigned to exactly one batch, all batches satisfy the capacity restriction of the pickers, and the total distance traveled by the pickers is minimal. In order to collect the items of a batch, the pickers traverse the warehouse using a predefined routing strategy. We propose a branch-price-and-cut (BPC) algorithm for the exact solution of the OBP investigating the routing strategies traversal, return, midpoint, largest gap, combined, and optimal. The column-generation pricing problem is modeled as a shortest path problem with resource constraints (SPPRC) that can be adapted to handle the implications from nonrobust valid inequalities and branching decisions. The SPPRC pricing problem is solved by means of an effective labeling algorithm that relies on strong completion bounds. Capacity cuts and subset-row cuts are used to strengthen the lower bounds. Furthermore, we derive two BPC-based heuristics to identify high-quality solutions in short computation times. Extensive computational results demonstrate the effectiveness of the proposed methods. The BPC is faster by two orders of magnitude compared with the state-of-the-art exact approach and can solve to optimality hundreds of instances that were previously unsolved. The BPC-based heuristics are able to significantly improve the gaps reported for the state-of-the-art heuristic and provide hundreds of new best-known solutions.

Funding: This research was supported by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) [Grant 418727865]. This support is gratefully acknowledged.

Supplemental Material: The e-companion is available at https://doi.org/10.1287/trsc.2023.1198 .
philosophy of childhood and children's political participation: poli(s)phonic challenges
Authors: Matos Susana Brissos , Vieira Paula Alexandra
Published: March 2023

What challenges does the political participation of children pose to the Philosophy of Childhood? What challenges does the Philosophy of Childhood pose to children's political participation? This text is inspired by the idea that “research is not about enumerating situations, but making researchers lose their sleep”. It is divided into two distinct parts. In the first, we introduce the theoretical framework that orients our research group and our work with children in the philosophical research community. We posit a link between listening to children's voices, the conditions of listening, and the location of their political participation in public space. The second part is comprised of a creative illustrated narrative in the form of a dialogue. From the coast of what could be called the territory of political participation, two characters - Sentinel and Walker - discuss the waves of children that crash onto the territory. To what extent does creating space and time for listening to children open polyphonic movements and enable the construction of new forms of polis: poly(s)phonies? In what ways does the Philosophy of Childhood challenge itself in the creation of poly(s)phonies where the participation of children sets the tone? In what ways does the Philosophy of Childhood in turn challenge us to create poly(s)phonies?
Iron supplementation for iron-deficiency anaemia
Authors: McDonald Elissa M , Mousa Sara , Ram Felix S F
Published: March 2023

Background:

In recent years, iron supplementation has increased significantly because of the damaging systemic effects of iron deficiency anaemia (IDA) being reported. The standard first-line therapy is oral iron tablets, with over 70% of recipients experiencing gastrointestinal adverse effects.

Methods:

This recent review of high-quality literature compares the effectiveness and adverse effects of tablet and liquid forms of iron supplementation in patients with IDA.

Findings:

The evidence to date indicates that both forms of iron supplementation are equally effective. However, the literature consistently and strongly supports the use of the liquid form of iron supplementation (ferrous sulfate) over the tablet form (ferrous sulphate or ferrous fumarate) in terms of adverse effects.

Conclusions:

Healthcare professionals should consider recommending the use of liquid iron formulation for the management of IDA and switch patients to this form if they experience gastrointestinal adverse effects. This may help to effectively manage IDA.
Self-efficacy: A key coaching consideration for primary care
Authors: Leech Darren
Published: March 2023

Self-efficacy can provide the foundation for motivation, wellbeing and personal accomplishment. Darren Leech explains how coaching for self-efficacy could be relevant for primary care leaders working at practice, ‘place’ and system level in today's NHS