bluuebunny/crossref_metadata_2025_split huggingface dataset:
CDK2 regulates collapsed replication fork repair in CCNE1-amplified ovarian cancer cells via homologous recombination
Authors: Brown Victoria E , Moore Sydney L , Chen Maxine , House Nealia , Ramsden Philip , Wu Hsin-Jung , Ribich Scott , Grassian Alexandra R , Choi Yoon Jong 
Published: July 2023

Abstract
CCNE1 amplification is a common alteration in high-grade serous ovarian cancer and occurs in 15–20% of these tumors. These amplifications are mutually exclusive with homologous recombination deficiency, and, as they have intact homologous recombination, are intrinsically resistant to poly (ADP-ribose) polymerase inhibitors or chemotherapy agents. Understanding the molecular mechanisms that lead to this mutual exclusivity may reveal therapeutic vulnerabilities that could be leveraged in the clinic in this still underserved patient population. Here, we demonstrate that CCNE1-amplified high-grade serous ovarian cancer cells rely on homologous recombination to repair collapsed replication forks. Cyclin-dependent kinase 2, the canonical partner of cyclin E1, uniquely regulates homologous recombination in this genetic context, and as such cyclin-dependent kinase 2 inhibition synergizes with DNA damaging agents in vitro and in vivo. We demonstrate that combining a selective cyclin-dependent kinase 2 inhibitor with a DNA damaging agent could be a powerful tool in the clinic for high-grade serous ovarian cancer.
Phylogenetic signal in gut microbial community rather than in rodent metabolic traits
Authors: Zhang Xue-Ying , Khakisahneh Saeid , Liu Wei , Zhang Xinyi , Zhai Weiwei , Cheng Jilong , Speakman John R , Wang De-Hua 
Published: July 2023

Abstract
Host phylogeny and environment have all been implicated in shaping the gut microbiota and host metabolic traits of mammals. However, few studies have evaluated phylogeny-associated microbial assembly and host metabolic plasticity concurrently, and their relationships on both short-term and evolutionary timescales. We report that the branching order of a gut microbial dendrogram was nearly congruent with phylogenetic relationships of seven rodent species, and this pattern of phylosymbiosis was intact after diverse laboratory manipulations. Laboratory rearing, diet or air temperature (Ta) acclimation induced alterations in gut microbial communities, but could not override host phylogeny in shaping microbial community assembly. A simulative heatwave reduced core microbiota diversity by 26% in these species, and led to an unmatched relationship between the microbiota and host metabolic phenotypes in desert species. Moreover, the similarity of metabolic traits across species at different Tas was not correlated with phylogenetic distance. These data demonstrated that the gut microbial assembly showed strong concordance with host phylogeny and may be shaped by environmental variables, whereas host metabolic traits did not seem to be linked with phylogeny.
Enablers and barriers to mental health initiatives in construction SMEs
Authors: Blake H , Bullock H , Chouliara N 
Published: July 2023

Abstract

Background
Mental ill-health is prevalent in the construction industry, and workers in small- to medium-sized enterprises (SMEs) are at high risk. Knowledge about the implementation of mental health initiatives in construction SMEs is limited.

Aims
To explore enablers and barriers to implementing mental health initiatives within UK SME construction firms from the perspective of the business owners, directors and managers with responsibilities for workplace mental health.

Methods
Qualitative study involving semi-structured interviews conducted with company owners/managers with responsibilities for workforce mental health. Participants were sampled from construction SMEs in the UK.

Results
Eleven construction professionals were interviewed (10 men, 1 woman; aged 34–55 years, M = 40.6) representing UK SME construction firms that were micro (&lt;10 employees, n = 8), small (&lt;50 employees, n = 1) and medium (&lt;250 employees, n = 2) sized organizations. Reflexive thematic analysis generated four themes: (i) traditional views and macho culture, identified as barriers to implementation; (ii) mental health awareness, knowledge and education; (iii) valuing good mental health and (iv) a reactive or proactive approach to mental health, which all served as both enablers and barriers depending on perspective and context.

Conclusions
This study sheds light on an under-researched but high-risk category of workers experiencing poor mental health. We provide recommendations for policy and practice with a ‘call to action’ for SME owners, industry and policymakers to embark on workplace mental health implementation projects in SME settings.
Long-term Outcomes of Patients With HIV and Pneumocystis jirovecii Pneumonia in the Antiretroviral Therapy Era
Authors: Epling Brian P , Manion Maura , Sirajuddin Arlene , Laidlaw Elizabeth , Galindo Frances , Anderson Megan , Roby Gregg , Rocco Joseph M , Lisco Andrea , Sheikh Virginia , Kovacs Joseph A , Sereti Irini 
Published: July 2023

Abstract

Background
Pneumocystis jirovecii pneumonia (PCP) is one of the most frequent opportunistic infections in people with HIV (PWH). However, there are limited data on long-term outcomes of PCP in the antiretroviral therapy (ART) era.

Methods
We conducted a secondary analysis of 2 prospective studies on 307 PWH, 81 with prior PCP, with a median follow-up of 96 weeks. Laboratory data were measured at protocol-defined intervals. We reviewed clinically indicated chest computerized tomography imaging in 63 patients with prior PCP at a median of 58 weeks after PCP diagnosis and pulmonary function tests (PFTs) of patients with (n = 10) and without (n = 14) prior PCP at a median of 18 weeks after ART initiation.

Results
After 96 weeks of ART, PWH with prior PCP showed no significant differences in laboratory measurements, including CD4 count, when compared with those without prior PCP. Survival rates following ART initiation were similar. However, PWH with prior PCP had increased evidence of restrictive lung pathology and diffusion impairment in PFTs. Furthermore, on chest imaging, 13% of patients had bronchiectasis and 11% had subpleural cysts. Treatment with corticosteroids was associated with an increased incidence of cytomegalovirus disease (odds ratio, 2.62; P = .014).

Conclusions
PCP remains an important opportunistic infection in the ART era. While it did not negatively affect CD4 reconstitution, it could pose an increased risk for incident cytomegalovirus disease with corticosteroid treatment and may cause residual pulmonary sequelae. These findings suggest that PCP and its treatment may contribute to long-term morbidity in PWH, even in the ART era.
Plasma diagnostics and Alfvén wave heating of solar prominences by multiwavelength observations
Authors: Hashimoto Yuki , Ichimoto Kiyoshi , Huang Yuwei 
Published: July 2023

Abstract
Solar prominences are cool and dense plasma supported by the magnetic field in the solar corona. They are composed of fine-scale structures called threads. Prominences are heated by the incident radiation from the solar atmosphere, but previous studies have shown that additional heating is necessary to maintain the temperature of prominences of about 104 K. This study aims to investigate quantitatively the mechanical heating of the prominences from observations. We performed spectroscopic observations of prominences in Hα (6563 Å), Hβ (4861 Å), and Ca ii IR (8542 Å) with the Domeless Solar Telescope at Hida observatory. The plasma parameters of the prominences are estimated by fittings of line profiles using the single-slab model and by solving the statistical equilibrium equation. By assuming that the turbulent motion is the manifestation of propagating Alfvén waves, net radiative losses and Alfvén wave energy flux in the prominences are estimated from these parameters. As a result, it was found that the energy flux by Alfvén waves is sufficient to compensate for the net radiative losses in most regions of the central part of the prominences. On the other hand, Alfvén wave energy flux tends to be insufficient at the outer part of prominences. In such regions, another heating mechanism such as enthalpy flux of mixing with coronal plasma needs to be considered.
Health as Complete Well-Being: The WHO Definition and Beyond
Authors: Schramme Thomas 
Published: July 2023

Abstract
The paper defends the World Health Organisation (WHO) definition of health against widespread criticism. The common objections are due to a possible misinterpretation of the word complete in the descriptor of health as ‘complete physical, mental and social well-being’. Complete here does not necessarily refer to perfect well-being but can alternatively mean exhaustive well-being, that is, containing all its constitutive features. In line with the alternative reading, I argue that the WHO definition puts forward a holistic account, not a notion of perfect health. I use historical and analytical evidence to defend this interpretation. In the second part of the paper, I further investigate the two different notions of health (holistic health and perfect health). I argue that both ideas are relevant but that the holistic interpretation is more adept for political aims.
Titrating CD47 by mismatch CRISPR-interference reveals incomplete repression can eliminate IgG-opsonized tumors but limits induction of antitumor IgG
Authors: Hayes Brandon H , Zhu Hui , Andrechak Jason C , Dooling Lawrence J , Discher Dennis E 
Published: July 2023

Abstract
Phagocytic elimination of solid tumors by innate immune cells seems attractive for immunotherapy, particularly because of the possibilities for acquired immunity. However, the approach remains challenging, with blockade of the macrophage checkpoint CD47 working in immunodeficient mice and against highly immunogenic tumors but not in the clinic where tumors are poorly immunogenic. Even when mouse tumors of poorly immunogenic B16F10 melanoma are opsonized to drive engulfment with a suitable monoclonal antibody (mAb), anti-CD47 blockade remains insufficient. Using both in vitro immuno-tumoroids and in vivo mouse models, we show with CRISPR interference (CRISPRi) that a relatively uniform minimum repression of CD47 by 80% is needed for phagocytosis to dominate net growth when combined with an otherwise ineffective mAb (anti-Tyrp1). Heterogeneity enriches for CD47-high cells, but mice that eliminate tumors generate prophagocytic IgGs that increase in titer with CD47 repression and with tumor accumulation of macrophages, although deeper repression does not improve survival. Given well-known limitations of antibody permeation into solid tumors, our studies clarify benchmarks for CD47 disruption that should be more clinically feasible and safer but just as effective as complete ablation. Additionally, safe but ineffective opsonization in human melanoma trials suggests that combinations with deep repression of CD47 could prove effective and initiate durable immunity.
Effects for global agriculture of country-specific climate policy regimes with a focus on methane
Authors: Mittenzwei Klaus , Hristov Jordan , Pérez-Domínguez Ignacio , Witzke Peter 
Published: July 2023

Abstract
While countries have agreed in the Paris-agreement on common rules to report greenhouse gas emissions, the design of domestic climate policy regimes remains in the national domain. This may cause different carbon prices for climate gasses across countries, between a country's emission sectors, and within the same sector. Our focus is on methane, which is a major emitter from agriculture, but also linked to livestock farming which is a core activity in agriculture worldwide. We analyse the potential effects of domestic carbon pricing regimes for agriculture in a non-cooperative game theoretic setting using a global agricultural sector model. Our results indicate no ‘race to the bottom’ to apply carbon pricing regimes that result in lowest implicit carbon prices for methane. Enforcing a uniform regime can reduce additional global warming with up to 0.02 °C, but runs the risk of agreeing to lower emission cuts than a nationally determined choice would suggest.
Primary central nervous system lymphoma (PCNSL) in older patients
Authors: Bertucci Alexandre , Harlay Vincent , Chinot Olivier , Tabouret Emeline 
Published: July 2023

Introduction
Primary central nervous system lymphoma (PCNSL) is a rare, chemo and radio-sensitive tumor limited to the central nervous system. The incidence of PCSNL increases notably in the elderly population which represented approximately half of the patients. The limit of ‘elderly’ population remained debated and nonuniform, including 60 years as a cutoff for brain radiotherapy, 65 years for autologous stem-cell transplantation, and 70 years for the last clinical trials. Current therapeutic options include first line treatment based on high-dose methotrexate based polychemotherapy, consolidation chemotherapy, and adapted autologous stem cell transplantation for highly selected patients. At relapse, single agent targeted therapies or salvage chemotherapy followed by intensive consolidation are promising therapeutic options. Nevertheless, improving management of elderly patients is an urgent medical need that currently remains unresolved.

Objective
We will focus on elderly patients with PCNSL and their specificities including clinical presentations, available therapeutic options and adaptations to be made.

Conclusion
To improve survival, it will be necessary to personalized and adapt the treatments, to each patient and his comorbidities, to increase their effectiveness and limit their toxicity in this frail population. Finally, inclusion of these patients in clinical trials is one of the major challenges to significantly change PCNSL elderly patient prognosis.
Postoperative Increase in Intraocular Pressure After Penetrating Keratoplasty and Descemet Stripping Automated Endothelial Keratoplasty in Asian Patients
Authors: Kurita Junki , Hayashi Takahiko , Shimizu Toshiki , Sunouchi Chihiro , Hara Yusuke , Kobayashi Akira , Yamagami Satoru 
Published: July 2023

Purpose:
We compared factors that contribute to postoperative intraocular pressure (IOP) elevation after penetrating or Descemet stripping automated endothelial keratoplasty in Asian patients.

Methods:
Consecutive patients who underwent corneal transplantation by penetrating or Descemet stripping automated endothelial keratoplasty were included. IOP was recorded preoperatively and at every postoperative visit for 2 years. Demographic factors and preoperative and maximum postoperative IOP were statistically compared between the groups. IOP elevation risk factors were identified using the log-rank test and multivariate Cox proportional hazards regression analysis with time-dependent covariates.

Results:
Twenty-two patients with penetrating keratoplasty (13 men, 9 women; aged 55.0 ± 21.6 years) and 46 patients with Descemet stripping automated endothelial keratoplasty (20 men, 26 women; aged 76.7 ± 10.7 years) were included. Preoperative IOP was lower in eyes treated with penetrating keratoplasty (10.5 ± 3.6 mm Hg, measurements of 2 cases were not recorded) than in eyes treated with Descemet stripping automated endothelial keratoplasty (14.0 ± 3.4 mm Hg, P < 0.001). Postoperative maximum IOP was higher in penetrating keratoplasty (21.1 ± 6.2 mm Hg) than in Descemet stripping automated endothelial keratoplasty (15.8 ± 5.3, P < 0.001). Intraocular pressure was elevated in 11 (50%) and 9 (19.6%) eyes treated with penetrating and Descemet stripping automated endothelial keratoplasty, respectively. Penetrating keratoplasty was identified as a risk factor for IOP elevation.

Conclusions:
Postoperative IOP elevation was more likely to occur after penetrating keratoplasty than after Descemet stripping automated endothelial keratoplasty. Postoperative IOP should be carefully monitored and managed in patients after corneal transplantation.
Defining the Value of Breast Reconstruction Surgeons: Quantifying Clinical Encounter and Operative Volume at an Academic Center
Authors: Sergesketter Amanda R. , Mundy Lily R. , Langdell Hannah C. , Shammas Ronnie L. , Geng Yisong , Rezak Kristen , Sisk Geoffroy C. , Phillips Brett T. , Hollenbeck Scott T. 
Published: July 2023

Background:
Despite growing rates of postmastectomy breast reconstruction, the time contribution of breast reconstruction surgeons in comprehensive breast cancer care is often poorly accounted for by hospital and healthcare systems. This study models encounter volume and operative time utilization of breast reconstruction surgeons among patients undergoing postmastectomy breast reconstruction.

Methods:
All clinical encounters and operative time from a consecutive sample of breast cancer patients undergoing mastectomy and reconstruction were analyzed. Encounter volume and operative time utilization less than or equal to 4 years after diagnosis were modeled over time.

Results:
A total of 5057 breast cancer encounters were analyzed. Mean (SD) clinical encounter volume was 45.9 (28.5) encounters per patient, with encounter volume varying by specialty [plastic surgery: 16.5; medical oncology: 15.9; breast surgery: 7.2; radiation oncology: 6.3 mean encounters]. Receipt of adjuvant radiation, neoadjuvant chemotherapy, and major complications during reconstruction predicted higher encounter volume. Mean (SD) operative time utilization was 702 (317) minutes per patient [plastic surgery: 547 (305); breast surgery: 155 (71) minutes]. While both encounter volume and operative time for radiation oncologists and breast surgeons, respectively, were concentrated in the first year after diagnosis, medical oncologists and plastic surgeons sustained high clinical and operative time utilization 3 years after breast cancer diagnosis.

Conclusions:
Encounter volume and operative time utilization with breast reconstruction surgeons persist 3 years after a breast cancer diagnosis and are tied to treatment characteristics and incidence of reconstruction complications. Institutional- and system-level resource allocation must account for the complex and lengthy duration of care inherent to breast reconstruction care.
Sensate Reverse Medial Plantar Flap for Reliable Forefoot Reconstruction with Flow-through Anterolateral Thigh Flap
Authors: Murakami Masami , Hori Keijiro , Niimi Yosuke , Nagashima Yoji , Sakurai Hiroyuki 
Published: July 2023

Summary:
A reverse medial plantar flap is a major option for reconstructing the plantar forefoot. However, reconstruction of the distal forefoot stretches the vessels, causing tightness, and the skin graft to the donor site adds pressure to the vessel, precipitating venous congestion. We used a reverse medial plantar flap to reconstruct the lateral distal forefoot with a flow-through of the anterolateral thigh (ALT) flap for donor site coverage to maintain physiological and stable blood flow. A 74-year-old woman presented to our hospital with a 20-year history of left forefoot skin tumor. The tumor was resected, and histological examination revealed porocarcinoma in the cystic poroid hidradenoma. Additional excision was performed, and the defect area was covered with a biodegradable artificial dermis. The skin defect of the lateral distal plantar area was reconstructed with a reverse medial plantar flap with a reverse flow Y-V pedicle extension method, and the donor site was reconstructed with an ALT flap interposing the lateral circumflex femoral artery with the transected posterior tibial artery. The flap was completely engrafted without any complications, including arterial ischemia or venous congestion, during or after surgery. A distally based reverse medial plantar flap with a reverse flow Y-V pedicle extension method and flow-through of the ALT flap should be considered for the reconstruction of the lateral distal forefoot with a large defect. This method can maximize flap extension and maintain stable arterial inflow and venous drainage without the major complications of venous congestion.
Minimally Invasive Mandibular Microsurgery: A Systematic Review and Meta-analysis
Authors: Godbe Kerilyn N. , O’Connor Michaela K. , Sinik Lauren M. , Vance Dylan T. , Nazir Niaman , Garg Ravi K. 
Published: July 2023

Background:
Microsurgical advances have led to minimally invasive approaches for mandibular reconstruction. Currently, no resource compares all minimally invasive microvascular mandibular reconstruction (MIMMR) treatment options.

Methods:
All known cases of MIMMR were identified following the Preferred Reporting Items for Systematic Reviews, Meta-Analyses guidelines, and our own surgical experience. Patient demographics, MIMMR type [submandibular (SM), modified facelift/retroauricular (MFL/RA), or intraoral (IO)], methodology, and clinical outcomes were analyzed with the Fisher exact and Kruskal-Wallis tests.

Results:
Forty-seven patients underwent MIMMR. Ameloblastoma was the most common pathology treated using all approaches, and MFL/RA was the only approach used to treat squamous cell carcinoma (P = 0.0103). Reconstruction was reported for large, bilateral defects only via the SM or IO approach (P = 0.0216). The iliac crest or fibula was used as a donor site. The facial artery was the most common recipient vessel using the IO and SM approaches, whereas the superior thyroid and external carotid vessels were the most common in the MFL/RA approach (P < 0.0001). Virtual planning was used in all cases performed via an IO approach, 80.0% of cases using an SM approach, and no MFL/RA cases (P < 0.0001). Good aesthetic and functional outcomes were reported for every patient, and there was no difference in complication rates (P = 0.2880).

Conclusions:
Minimally invasive approaches are safe and effective treatment options for patients requiring mandibular microsurgery, usually in the setting of benign pathology. The IO and SM approaches usually rely on the facial vessels, whereas the MFL/RA approach permits access to the superior thyroid and external carotid vessels and cervical lymphadenectomy.