bluuebunny/crossref_metadata_2025_split huggingface dataset:
Detecting and preventing child maltreatment in primary care and PHNs’ role—a cross-sectional study
Authors: Midtsund Astrid Durdei , Henriksen Lena , Lukasse Mirjam , Valla Lisbeth 
Published: June 2024

Abstract
Background
Child maltreatment is a global problem that puts children at risk of mental illness, substance abuse, and premature death. Interdisciplinary collaboration is important in preventing and detecting child maltreatment. In Norway, children undergo universal preventive health assessments and receive complimentary follow-up care from specialized public health nurses in child and family health clinics. These nurses conduct regular check-ups and home visits to monitor children for signs of maltreatment.

Objective
The objective of this study is to describe how public health nurses at child and family health clinics follow the National Clinical Guidelines to prevent and detect child maltreatment, with a particular focus on clinical procedures and interdisciplinary collaboration. Furthermore, we aim to determine factors that are associated with identification of child maltreatment.

Design
A cross-sectional online survey was conducted among public health nurses working in primary care between October 24th and December 31st, 2022. Public health nurses who worked with children aged 0–5 years and had consultations with families were eligible to participate, resulting in 554 responses. The study employed descriptive analysis, including frequency, percentage and mean, as well as a two-step logistic regression analysis. The study was approved by the relevant authority, and informed consent was obtained through questionnaire completion.

Results
The public health nurses in this study displayed strong adherence to the guidelines and utilized various comprehensive assessment procedures to monitor child well-being, growth, and development. However, there was limited and infrequent collaboration with other professionals, such as child protection services, general practitioners, and hospitals. Most public health nurses reported occasional suspicion of child maltreatment, with age and years of experience in child and family clinics influencing these suspicions. Older public health nurses were more likely to suspect physical violence, while those with less than two years of experience reported less experience in suspecting maltreatment. Additional education increased the probability of suspecting sexual violence.

Conclusions
This study provides insights into the practices of public health nurses in Norway regarding the detection and prevention of child maltreatment in child and family clinics. While adherence to guidelines is strong, suspicion of maltreatment is relatively rare. Collaboration across agencies is crucial in addressing child maltreatment. Age and experience may influence the detection of maltreatment. Improved collaboration, targeted guidelines, and ongoing professional development are needed to enhance child protection.
Safety and efficacy analysis of neoadjuvant pertuzumab, trastuzumab and standard chemotherapy for HER2–positive early breast cancer: real–world data from NeoPowER study
Authors: Canino Fabio , Barbolini Monica , De Giorgi Ugo , Fontana Tommaso , Gaspari Valeria , Gianni Caterina , Gianni Lorenzo , Maestri Antonio , Minichillo Santino , Moscetti Luca , Mura Antonella , Nicoletti Stefania Vittoria Luisa , Omarini Claudia , Pagani Rachele , Sarti Samanta , Toss Angela , Zamagni Claudio , Cuoghi Costantini Riccardo , Caggia Federica , Antonelli Giuseppina , Baglio Federica , Belluzzi Lorenzo , Martinelli Giulio , Natalizio Salvatore , Ponzoni Ornella , Dominici Massimo , Piacentini Federico 
Published: June 2024

Abstract
Background
The addition of pertuzumab (P) to trastuzumab (H) and standard chemotherapy (CT) as neoadjuvant treatment (NaT) for patients with HER2 + breast cancer (BC), has shown to increase the pathological complete response (pCR) rate, without main safety concerns. The aim of NeoPowER trial is to evaluate safety and efficacy of P + H + CT in a real–world population.

Methods
We retrospectively reviewed the medical records of stage II–III, HER2 + BC patients treated with NaT: who received P + H + CT (neopower group) in 5 Emilia Romagna institutions were compared with an historical group who received H + CT (control group). The primary endpoint was the safety, secondary endpoints were pCR rate, DRFS and OS and their correlation to NaT and other potential variables.

Results
260 patients were included, 48% received P + H + CT, of whom 44% was given anthraciclynes as part of CT, compared to 83% in the control group. The toxicity profile was similar, excluding diarrhea more frequent in the neopower group (20% vs. 9%). Three patients experienced significant reductions in left ventricular ejection fraction (LVEF), all receiving anthracyclines. The pCR rate was 46% (P + H + CT) and 40% (H + CT) (p = 0.39). The addition of P had statistically correlation with pCR only in the patients receiving anthra-free regimens (OR = 3.05,p = 0.047). Preoperative use of anthracyclines (OR = 1.81,p = 0.03) and duration of NaT (OR = 1.18,p = 0.02) were statistically related to pCR. 12/21 distant-relapse events and 14/17 deaths occurred in the control group. Patients who achieve pCR had a significant increase in DRFS (HR = 0.23,p = 0.009).

Conclusions
Adding neoadjuvant P to H and CT is safe. With the exception of diarrhea, rate of adverse events of grade > 2 did not differ between the two groups. P did not increase the cardiotoxicity when added to H + CT, nevertheless in our population all cardiac events occurred in patients who received anthracycline-containing regimens. Not statistically significant, higher pCR rate is achievable in patients receiving neoadjuvant P + H + CT. The study did not show a statistically significant correlation between the addition of P and long-term outcomes.
Carcinoma in situ within the bladder trigone with an isolated metastasis to the prostate without involvement of prostatic urethra: a unique case report
Authors: Batha Omran , Aldolly Ahmed , Alsaffaf Yousef , Hamsho Suaad , Atia Mohammad , Salmeh Fayez , Alia Louei 
Published: June 2024

Abstract
Background
Carcinoma in situ of the bladder is a high-grade cancer that originates in the superficial layer of the bladder. It has the potential to invade nearby organs, and it can spread through blood and lymphatic circulation to distant parts of the body.

Case presentation
A 58-year-old non-smoker male presented with gross and microscopic hematuria. His family history included his father’s recent bladder cancer. Initial investigations showed hematuria, inflammation, negative urine culture, digital rectal examination revealed an enlarged right lobe of the prostate, and an elevated Prostate-Specific Antigen level. Histopathological examination of samples taken from the bladder mucosa and the prostate confirmed urothelial carcinoma in situ in the bladder and prostate. Further evaluation revealed no other metastasis. The tumor was classified as T4aN0M0. The patient underwent radical cystoprostatectomy and histopathological examination showed that the tumor invading the muscularis propria of the bladder as well as the prostatic glands, but no malignancy was found in prostatic urethra and other areas. The patient was discharged three weeks post-operation and completed on adjuvant chemotherapy consisting of Gemcitabine, and Cisplatin to prevent of relapse. The patient is currently in a good healthy.

Conclusion
The occurrence of bladder cancer metastasizing to the prostate without involving the prostatic urethra is uncommon and requires precise diagnostic techniques for accurate tumor classification. Early management is advised to enhance the prognosis for the patient.
A comparative study of microbial changes in dental plaque before and after single- and multiappointment treatments in patients with severe early childhood caries
Authors: Ma Shi Ying , Zhou Qing Nan , Cai Shuang , Zhou Yan , Zhang Xiao Yu , Feng Xiao Yu , Diao Shu , Xi Jin Qiu , Yu Guo Xia , Shang Jia Jian , Yang Ning Yan 
Published: June 2024

Abstract
Background
The status of dental caries is closely related to changes in the oral microbiome. In this study, we compared the diversity and structure of the dental plaque microbiome in children with severe early childhood caries (S-ECC) before and after general anaesthesia and outpatient treatment.

Methods
Forty children aged 3 to 5 years with S-ECC who had completed whole-mouth dental treatment under general anaesthesia (C1) or in outpatient settings (C2) were selected, 20 in each group. The basic information and oral health status of the children were recorded, and the microbial community structure and diversity of dental plaque before treatment (C1, C2), the day after treatment(C2_0D), 7 days after treatment (C1_7D, C2_7D), 1 month after treatment (C1_1M, C2_1M), and 3 months after treatment (C1_3M, C2_3M) were analysed via 16 S rRNA high-throughput sequencing technology.

Results
(1) The alpha diversity test showed that the flora richness in the multiappointment group was significantly greater at posttreatment than at pretreatment (P < 0.05), and the remaining alpha diversity index did not significantly differ between the 2 groups (P > 0.05). The beta diversity analysis revealed that the flora structures of the C1_7D group and the C2_3M group were significantly different from those of the other time points within the respective groups (P < 0.05). (2) The core flora existed in both the pre- and posttreatment groups, and the proportion of their flora abundance could be altered depending on the caries status of the children in both groups. Leptotrichia abundance was significantly (P < 0.05) lower at 7 days posttreatment in both the single- and multiappointment groups. Corynebacterium and Corynebacterium_matruchotii were significantly more abundant in the C1_1M and C1_3M groups than in the C1 and C1_7D groups (P < 0.05). Streptococcus, Haemophilus and Haemophilus_parainfluenzae were significantly more abundant in the C1_7D group than in the other groups (P < 0.05).

Conclusion
A single session of treatment under general anaesthesia can cause dramatic changes in the microbial community structure and composition within 7 days after treatment, whereas treatment over multiple appointments may cause slow changes in oral flora diversity.
Health care providers’ perspectives on the need for palliative care in Upper Egypt: a descriptive exploratory study including children and adult patients
Authors: Osman Atiat , Horvick Savannah Gail , Dias Nancy 
Published: June 2024

Abstract
Background
Only four centers in Egypt provide Palliative Care (PC) for adult cancer patients and one provides care for pediatric cancer patients. While PC is not widely utilized in Egypt, this study aims to assess patients’ need for PC from the providers’ perspective. The primary objectives were to assess providers’ knowledge about PC, understand patients’ needs, and compare children’s and adults’ needs for PC.

Methods
A descriptive exploratory design was utilized. Patients were recruited from a cancer center in Qena Governorate, Egypt. All 108 nurses and physicians in the cancer center were interviewed to assess their perspectives about PC and patients’ need for it.

Results
Of the 108 care providers, more than 60% of the providers were not familiar with the concept of PC and did not participate in related activities, and more than 77% did not receive any training on the topic. All the providers reported there is no specific policy for end-of-life care. More than 60% of the providers responded that their patients do not need PC as the providers believe that PC provided only for end-stage patients. 50% of the providers see that PC has benefits such as pain relief and symptom management. No major differences were noted between pediatric and adult PC needs.

Conclusion
The results of this study provide foundational evidence of providers’ lack of experience with and understanding of palliative care. This deficit is creating a barrier to providing palliative care in Egypt.
Bi-directionalized promoter systems allow methanol-free production of hard-to-express peroxygenases with Komagataella Phaffii
Authors: Besleaga Mihail , Zimmermann Christian , Ebner Katharina , Mach Robert L. , Mach-Aigner Astrid R. , Geier Martina , Glieder Anton , Spadiut Oliver , Kopp Julian 
Published: June 2024

Abstract
Background
Heme-incorporating peroxygenases are responsible for electron transport in a multitude of organisms. Yet their application in biocatalysis is hindered due to their challenging recombinant production. Previous studies suggest Komagataella phaffi to be a suitable production host for heme-containing enzymes. In addition, co-expression of helper proteins has been shown to aid protein folding in yeast. In order to facilitate recombinant protein expression for an unspecific peroxygenase (AnoUPO), we aimed to apply a bi-directionalized expression strategy with Komagataella phaffii.

Results
In initial screenings, co-expression of protein disulfide isomerase was found to aid the correct folding of the expressed unspecific peroxygenase in K. phaffi. A multitude of different bi-directionalized promoter combinations was screened. The clone with the most promising promoter combination was scaled up to bioreactor cultivations and compared to a mono-directional construct (expressing only the peroxygenase). The strains were screened for the target enzyme productivity in a dynamic matter, investigating both derepression and mixed feeding (methanol-glycerol) for induction. Set-points from bioreactor screenings, resulting in the highest peroxygenase productivity, for derepressed and methanol-based induction were chosen to conduct dedicated peroxygenase production runs and were analyzed with RT-qPCR. Results demonstrated that methanol-free cultivation is superior over mixed feeding in regard to cell-specific enzyme productivity. RT-qPCR analysis confirmed that mixed feeding resulted in high stress for the host cells, impeding high productivity. Moreover, the bi-directionalized construct resulted in a much higher specific enzymatic activity over the mono-directional expression system.

Conclusions
In this study, we demonstrate a methanol-free bioreactor production strategy for an unspecific peroxygenase, yet not shown in literature. Hence, bi-directionalized assisted protein expression in K. phaffii, cultivated under derepressed conditions, is indicated to be an effective production strategy for heme-containing oxidoreductases. This very production strategy might be opening up further opportunities for biocatalysis.
An urgent need for community lot testing of lateral flow fentanyl test strips marketed for harm reduction in Northern America
Authors: Lieberman Marya , Badea Adina , Desnoyers Charlie , Hayes Kathleen , Park Ju Nyeong 
Published: June 2024

Abstract
Background
Fentanyl test strips (FTS) are lateral flow immunoassay strips designed for detection of ng/mL levels of fentanyl in urine. In 2021, the US Centers for Disease Control and the Substance Abuse and Mental Health Administration stated that federal funds could be used for procurement of FTS for harm reduction strategies approved by the government such as drug checking. The market for FTS has expanded rapidly in the US and Canada. However, there is no regulatory oversight by either government to ensure proper function of FTS that are being marketed for drug checking.

Main body
Many brands of FTS have rapidly entered the harm reduction market, creating concerns about the reproducibility and accuracy of their performance from brand to brand and lot to lot. Some examples are provided in this Comment. Similar problems with product quality were observed in the mid 2000’s when lateral flow immunoassays for malaria were funded in many countries and again in 2020, when COVID-19 tests were in huge demand. The combination of high demand and low levels of regulation and enforcement led some manufacturers to join the goldrush without adequate field testing or quality assurance. We argue that the harm reduction community urgently needs to set a lot checking program in place. A set of simple protocols for conducting the tests and communicating the results have been developed, and are described in the following Perspectives paper in this issue.

Conclusion
In the absence of governmental regulation and enforcement, the harm reduction community should implement a FTS lot checking program. Based on previous experience with the malaria diagnostic lot checking program, this inexpensive effort could identify products that are not suitable for harm reduction applications and provide valuable feedback to manufacturers. Dissemination of the results will help harm reduction organizations to ensure that FTS they use for drug checking are fit for the purpose.
Gut microbiota-derived acetate attenuates lung injury induced by influenza infection via protecting airway tight junctions
Authors: Hu Lei , Sun Li , Yang Chun , Zhang Da-Wei , Wei Yuan-Yuan , Yang Ming-Ming , Wu Hui-Mei , Fei Guang-He 
Published: June 2024

Abstract
Background
Gut microbiota (GM) have been implicated as important regulators of gastrointestinal symptom which is commonly occurred along with respiratory influenza A virus (IAV) infection, suggesting the involvement of the gut-to-lung axis in a host’s response to IAV. IAV primarily destroys airway epithelium tight junctions (TJs) and consequently causes acute respiratory disease syndrome. It is known that GM and their metabolism produce an anti-influenza effect, but their role in IAV-induced airway epithelial integrity remains unknown.

Methods
A mouse model of IAV infection was established. GM were analyzed using 16S rRNA gene sequencing, and short-chain fatty acids (SCFAs) levels were measured. GM depletion and fecal microbiota transplantation (FMT) were conducted to validate the role of GM in IAV infection. A pair-feeding experiment was conducted to reveal whether IAV-induced GM dysbiosis is attributed to impaired food intake. Furthermore, human bronchial epithelial (HBE) cells were cocultured with IAV in the presence or absence of acetate. TJs function was analyzed by paracellular permeability and transepithelial electronic resistance (TEER). The mechanism of how acetate affects TJs integrity was evaluated in HBE cells transfected with G protein-coupled receptor 43 (GPR43) short hairpin RNA (shRNA).

Results
IAV-infected mice exhibited lower relative abundance of acetate-producing bacteria (Bacteroides, Bifidobacterium, and Akkermansia) and decreased acetate levels in gut and serum. These changes were partly caused by a decrease in food consumption (due to anorexia). GM depletion exacerbated and FMT restored IAV-induced lung inflammatory injury. IAV infection suppressed expressions of TJs (occludin, ZO-1) leading to disrupted airway epithelial barrier function as evidenced by decreased TEER and increased permeability. Acetate pretreatment activated GPR43, partially restored IAV-induced airway epithelial barrier function, and reduced inflammatory cytokines levels (TNF-α, IL-6, and IL-1β). Such protective effects of acetate were absent in HBE cells transfected with GPR43 shRNA. Acetate and GPR43 improved TJs in an AMP-activated protein kinase (AMPK)-dependent manner.

Conclusion
Collectively, our results demonstrated that GM protected airway TJs by modulating GPR43-AMPK signaling in IAV-induced lung injury. Therefore, improving GM dysbiosis may be a potential therapeutic target for patients with IAV infection.
Cystatin F attenuates neuroinflammation and demyelination following murine coronavirus infection of the central nervous system
Authors: Syage Amber R. , Pachow Collin , Murray Kaitlin M. , Henningfield Caden , Fernandez Kellie , Du Annie , Cheng Yuting , Olivarria Gema , Kawauchi Shimako , MacGregor Grant R. , Green Kim N. , Lane Thomas E. 
Published: June 2024

Abstract
Background
Cystatin F is a secreted lysosomal cysteine protease inhibitor that has been implicated in affecting the severity of demyelination and enhancing remyelination in pre-clinical models of immune-mediated demyelination. How cystatin F impacts neurologic disease severity following viral infection of the central nervous system (CNS) has not been well characterized and was the focus of this study. We used cystatin F null-mutant mice (Cst7-/-) with a well-established model of murine coronavirus-induced neurologic disease to evaluate the contributions of cystatin F in host defense, demyelination and remyelination.

Methods
Wildtype controls and Cst7-/- mice were intracranially (i.c.) infected with a sublethal dose of the neurotropic JHM strain of mouse hepatitis virus (JHMV), with disease progression and survival monitored daily. Viral plaque assays and qPCR were used to assess viral levels in CNS. Immune cell infiltration into the CNS and immune cell activation were determined by flow cytometry and 10X genomics chromium 3’ single cell RNA sequencing (scRNA-seq). Spinal cord demyelination was determined by luxol fast blue (LFB) and Hematoxylin/Eosin (H&E) staining and axonal damage assessed by immunohistochemical staining for SMI-32. Remyelination was evaluated by electron microscopy (EM) and calculation of g-ratios.

Results
JHMV-infected Cst7-/- mice were able to control viral replication within the CNS, indicating that cystatin F is not essential for an effective Th1 anti-viral immune response. Infiltration of T cells into the spinal cords of JHMV-infected Cst7-/- mice was increased compared to infected controls, and this correlated with increased axonal damage and demyelination associated with impaired remyelination. Single-cell RNA-seq of CD45 + cells enriched from spinal cords of infected Cst7-/- and control mice revealed enhanced expression of transcripts encoding T cell chemoattractants, Cxcl9 and Cxcl10, combined with elevated expression of interferon-g (Ifng) and perforin (Prf1) transcripts in CD8 + T cells from Cst7-/- mice compared to controls.

Conclusions
Cystatin F is not required for immune-mediated control of JHMV replication within the CNS. However, JHMV-infected Cst7-/- mice exhibited more severe clinical disease associated with increased demyelination and impaired remyelination. The increase in disease severity was associated with elevated expression of T cell chemoattractant chemokines, concurrent with increased neuroinflammation. These findings support the idea that cystatin F influences expression of proinflammatory gene expression impacting neuroinflammation, T cell activation and/or glia cell responses ultimately impacting neuroinflammation and neurologic disease.