bluuebunny/crossref_metadata_2025_split huggingface dataset:
Stability considerations for drug-device combination products-21 CFR part 4 update
Authors: Latoz Christopher , Larkin Laure , Huynh-Ba Kim 
Published: May 2023

AbstractCombination products are therapeutic and diagnostic products that include two or more of the following: drug, biologic, and device. These products are needed for enhanced clinical outcomes and have more than one Mode of Action (MOA). Therefore, they require a more complex regulatory pathway and compliance with a minimum of two (2) sets of regulatory standards. In 2013, the 21 Code of Federal Regulations (CFR) Part 4 was published to clarify the applicable GMP regulations when drugs, devices, or biological products are included. The FDA (U.S. Food and Drug Administration) released additional guidance in 2017 to streamline the regulatory framework and provide transparency about demonstrating GMP compliance when multiple regulatory standards overlap. This paper summarizes the Current Good Manufacturing Practice (CGMP) requirements for drug-device combination products (Biologic combinations are not discussed in this paper). Emphasis is placed on considerations for structuring a compliant drug-device stability program, including the use of bracketing and matrixing the test schedule to support the establishment of the product expiry date and how legacy products can be evaluated to meet current standards.
Improved visualization of the bone-implant interface and osseointegration in ex vivo acetabular cup implants using photon-counting detector CT
Authors: Woisetschläger Mischa , Booij Ronald , Tesselaar Erik , Oei Edwin H. G. , Schilcher Jörg 
Published: May 2023

Abstract
Background
Successful osseointegration of joint replacement implants is required for long-term implant survival. Accurate assessment of osseointegration could enable clinical discrimination of failed implants from other sources of pain avoiding unnecessary surgeries. Photon-counting detector computed tomography (PCD-CT) provides improvements in image resolution compared to conventional energy-integrating detector CT (EID-CT), possibly allowing better visualization of bone-implant-interfaces and osseointegration. The aim of this study was to assess the quality of visualization of bone-implant-interfaces and osseointegration in acetabular cup implants, using PCD-CT compared with EID-CT.

Methods
Two acetabular implants (one cemented, one uncemented) retrieved during revision surgery were scanned using PCD-CT and EID-CT at equal radiation dose. Images were reconstructed using different reconstruction kernels and iterative strengths. Delineation of the bone-implant and bone-cement-interface as an indicator of osseointegration was scored subjectively for image quality by four radiologists on a Likert scale and assessed quantitatively.

Results
Delineation of bone-implant and bone-cement-interfaces was better with PCD-CT compared with EID-CT (p ≤ 0.030). The highest ratings were given for PCD-CT at sharper kernels for the cemented cup (PCD-CT, median 5, interquartile range 4.25–5.00 versus EID-CT, 3, 2.00–3.75, p < 0.001) and the uncemented cup (5, 4.00–5.00 versus 2, 2–2, respectively, p < 0.001). The bone-implant-interface was 35–42% sharper and the bone-cement-interface was 28–43% sharper with PCD-CT compared with EID-CT, depending on the reconstruction kernel.

Conclusions
PCD-CT might enable a more accurate assessment of osseointegration of orthopedic joint replacement implants.

Key points
• The bone-implant interface ex vivo showed superior visualization using photon-counting detector computed tomography (PCD-CT) compared to energy-integrating detector computed tomography.
• Harder reconstruction kernels in PCD-CT provide sharper images with lower noise levels.
• These improvements in imaging might make it possible to visualize osseointegration in vivo.
The foramen ovale: a keyhole to the brain? Computer simulations of percutaneous FO punctures
Authors: Brandstetter Maximilian , Mallouhi Ammar , Alesch François 
Published: May 2023

Abstract
Background
The percutaneous cannulation of the foramen ovale (FO) is implemented in treating trigeminal neuralgia, diagnosing temporal lobe epilepsy and biopsy petroclival lesions. This study dealt with the question whether it is possible to reach intracerebral structures with a puncture beyond the Gasserian Ganglion (GG) without bone destruction or perforating vascularity.

Methods
We considered the FO a natural keyhole and performed computer-simulated punctures through the right and left FO to eight intracerebral structures. Therefore, we took the Hartel and Submandibular (SM) approach as a starting point and planned trajectories with stereotactic planning software by using brain scans of ten patients.

Results
The simulated punctures with the Hartel approach directly reached the hippocampus (20 out of 20 trajectories), the lateral ventricle (15/20) and the amygdala (2/20). The pons was reached (20/20); however, the pontine vascularity was within the course. The trajectories to the thalamus (13/20) ran through the hippocampus or the mesencephalon. The simulated punctures with the SM approach directly reached the amygdala (18/20), the lateral ventricle (5/20) and the putamen (20/20). The trajectories to the nucleus caudatus (20/20) pierced the hippocampus, the putamen or the maxillary artery. The courses to the thalamus (7/20) ran through the hippocampus or the mesencephalon. The sinus cavernosus could not be reached with the Hartel or SM approach.

Conclusions
This study indicates that a percutaneous approach to the hippocampus, the lateral ventricle, the amygdala and the putamen is possible without harming major vessels or bone destruction. For a possible implementation of these trajectories in a clinical setting, it is necessary to prove these simulated punctures in cadaveric studies.
Influence of the traditional food culture of Ancient Egypt on the transition of cuisine and food culture of contemporary Egypt
Authors: Halawa Abdelhadi 
Published: May 2023

AbstractBecause of the largely arid desert landscape of Egypt, for millennia, Egyptians have been closely connected to living alongside the narrow fertile banks of the Nile River. Annually, melting snow cascading from the mountains in the highlands of the south triggers the Nile River to flood on its journey northbound toward Egypt. As the flood water recedes, it leaves in its wake a rich layer of fertile, volcanic dark soil deposits. The Egyptians mainly rely on this annual natural event to grow various staple food crops, including emmer wheat for making bread, vegetables for cooking molokhia, fruits, and legumes for making koshary. Further, the Nile River provides a source of drinking water, fishing, and raising livestock for meat and dairy products for making halloumi and kariesh cheeses. Ancient Egyptians devoted a sizable portion of Pharaonic history to food, both as nourishment and for the preparation for the mythical religious experience on the journey into eternal life. Food played an essential role in performing religious rites, mummification, coronation and wedding banquets, burial ceremonies, and particularly in preparation for entering eternal life in the afterlife. Because the ancient Egyptians meticulously kept descriptive records, there is a considerable body of archaeological evidence and hieroglyphic accounts regarding ancient Egyptian tangible food history and culture. However, ancient Egyptian food culture has not received adequate scholarly investigations as did the Pharaohs, Pyramids, and mummies. This article aims to examine the under-researched area of the influence of the traditional food culture of Ancient Egypt on the transition of the cuisine and food culture of contemporary Egypt, and how the Pharaohs employed food to achieve longevity during their life and prepare for successful admission into their afterlife. Three factors have contributed to the development and continuation of the 5000-year Egyptian food culture. First, the existence of the Nile River provides reliable, rich silted soil for growing various staple crops. Second, the annual inundation of the Nile River transports fresh layers of silt-rich fertile soil, which provides stable agriculture and supports cultivating various food crops and raising livestock. Third, as a result, of the first two factors, Egypt has been experiencing abundantly diverse staple food sources for millennia.
Noninvasive identification of molecular biomarkers of hepatocellular carcinoma in HCV-Egyptian patients
Authors: Daif Ahmed , Al-Azzawi Mahmood A. , Sakr Moustafa A. , Ismail Hisham A. , Gadallah Mahmoud 
Published: May 2023

Abstract

Background
This study was performed to investigate the expression of different biomarkers in patients with hepatocellular carcinoma and its connection with detective biomarkers. To achieve this objective, seventy subjects were examined in this study, sub-grouped to forty HCC patients and thirty HCV-affected patients with matched thirty healthy individuals. The study involved several groups of participants who were matched based on their age and gender.

Methods
The expression pattern of biomarkers was monitored by quantitative polymerase chain reaction (qRT-PCR). Finally, we utilized a ROC curve to investigate the predictive accurateness of those distinct biomarkers as well as a traditional tumor marker, AFP, in detecting HCC cases.

Results
The baseline biomarker expression levels were markedly greater in HCC patients than in those affected by HCV or healthy subjects. We stated that the sensitivity and the specificity of the different biomarkers alone did not improve than that of AFP alone. When comparing AFP with different biomarkers, the diagnostic validity improves only when combining with CK-1.

Conclusions
Overall, our results indicate that CK-1 mRNA expression could help as a noninvasive tumor biomarker for HCC prognosis and diagnosis when combining with AFP.
To be well or not to be well: compositional associations of physical activity, sedentary behaviour and sleep with mental well-being in Flemish adults aged 55+ years
Authors: Vanderlinden Julie , Biddle Gregory J. H. , Boen Filip , van Uffelen Jannique G. Z. 
Published: May 2023

AbstractBackgroundWell-being is a key aspect for healthy ageing and there is an established association between physical activity and well-being in ageing adults. Despite the recent interest in physical activity as part of a 24-h continuum also including sedentary behaviour and sleep, there is a lack of studies examining the link between these 24-h behaviours and well-being in older adults. Therefore, the aim of this study was twofold: (1) to describe 24-h behaviours and their associations with mental well-being in community dwelling adults aged 55+ years; and (2) to examine the theoretical changes in mental well-being if time were reallocated from one behaviour to another.MethodsThis was a cross-sectional study (n = 410). Daily time spent in sedentary behaviour, light and moderate-vigorous physical activity, and sleep was assessed using wrist-worn accelerometers during 6 days. Mental well-being was assessed using the 14-item Warwick-Edinburgh Mental Well-being Scale (WEMWBS). The association of 24-h behaviours and well-being was examined using crude and adjusted linear regression models with compositional data analysis procedures (aim 1). Associations between reallocations of five-minute intervals from five to 60 min between these behaviours and well-being were modelled using compositional isotemporal substitutions (aim 2).ResultsMean age (SD) was 71.3 (6.3) years and 71% were female. In 24-h, participants spent 5.66 h asleep, 13.88 h sedentary, 2.58 h in light intensity and 1,89 h in moderate-vigorous intensity physical activity. There were no statistically significant associations between 24-h behaviours and mental well-being in fully adjusted models (aim 1). Reallocations up to 30 min were not significantly associated with changes in well-being (aim 2). There were some statistically significant theoretical changes of up to 2 points on the WEMWBS with substitutions larger than 30 min.Discussion24-h behaviours and time reallocations between behaviours were not associated with better or worse well-being in community dwelling adults aged 55+ years. Considering well-being as a key aspect for healthy ageing, future public health research should continue to examine physical activity (both light and moderate-to-vigorous), sedentary behaviour, as well as sleep as a part of the 24-h continuum and its associations with mental health outcomes in older adults.Trial registrationThis trial was registered at ClinicalTrials.gov on 3th July, 2018 (Trial registration NCT03576209)
Lateral thinking in syndromic congenital cardiovascular disease
Authors: Kocere Agnese , Lalonde Robert L. , Mosimann Christian , Burger Alexa 
Published: May 2023

ABSTRACT
Syndromic birth defects are rare diseases that can present with seemingly pleiotropic comorbidities. Prime examples are rare congenital heart and cardiovascular anomalies that can be accompanied by forelimb defects, kidney disorders and more. Whether such multi-organ defects share a developmental link remains a key question with relevance to the diagnosis, therapeutic intervention and long-term care of affected patients. The heart, endothelial and blood lineages develop together from the lateral plate mesoderm (LPM), which also harbors the progenitor cells for limb connective tissue, kidneys, mesothelia and smooth muscle. This developmental plasticity of the LPM, which founds on multi-lineage progenitor cells and shared transcription factor expression across different descendant lineages, has the potential to explain the seemingly disparate syndromic defects in rare congenital diseases. Combining patient genome-sequencing data with model organism studies has already provided a wealth of insights into complex LPM-associated birth defects, such as heart-hand syndromes. Here, we summarize developmental and known disease-causing mechanisms in early LPM patterning, address how defects in these processes drive multi-organ comorbidities, and outline how several cardiovascular and hematopoietic birth defects with complex comorbidities may be LPM-associated diseases. We also discuss strategies to integrate patient sequencing, data-aggregating resources and model organism studies to mechanistically decode congenital defects, including potentially LPM-associated orphan diseases. Eventually, linking complex congenital phenotypes to a common LPM origin provides a framework to discover developmental mechanisms and to anticipate comorbidities in congenital diseases affecting the cardiovascular system and beyond.
A Systematic Review of Methods Used to Determine the Work of Breathing during Exercise
Authors: Cross Troy J. , Isautier Jennifer Mj , Kelley Eli F. , Hubbard Colin D. , Morris Sarah J. , Smith Joshua R. , Duke Joseph W. 
Published: May 2023

ABSTRACT

Introduction
Measurement of the work of breathing (Wb) during exercise provides useful insights into the energetics and mechanics of the respiratory muscles across a wide range of minute ventilations. The methods and analytical procedures used to calculate the Wb during exercise have yet to be critically appraised in the literature.

Purpose
The aim of this systematic review was to evaluate the quality of methods used to measure the Wb during exercise in the available literature.

Methods
We conducted an extensive search of 3 databases for studies that measured the Wb during exercise in adult humans. Data were extracted on participant characteristics, flow/volume and pressure devices, oesophageal pressure (Poes) catheters, and methods of Wb analysis.

Results
A total of 120 articles were included. Flow/volume sensors used were primarily pneumotachographs (n = 85, 70.8%), whereas the most common pressure transducer was of the variable reluctance type (n = 63, 52.5%). Oesophageal pressure was frequently obtained via balloon-tipped catheters (n = 114, 95.0%). Few studies mentioned calibration, frequency responses and dynamic compensation of their measurement devices. The most popular method of measuring the Wb was pressure-volume integration (n = 51, 42.5%), followed by the modified Campbell (n = 28, 23.3%) and Dean & Visscher diagrams (n = 26, 21.7%). Over one-third of studies did not report the methods used to process their pressure-volume data, and the majority (60.8%) of studies used the incorrect Wb units and/or failed to discuss the limitations of their Wb measurements.

Conclusions
The findings of this systematic review highlight the need for the development of a standardized approach for measuring Wb which is informative, practical, and accessible for future researchers.
Physical Activity and Nonalcoholic Fatty Liver Disease: A Roundtable Statement from the American College of Sports Medicine
Authors: STINE JONATHAN G. , LONG MICHELLE T. , COREY KATHLEEN E. , SALLIS ROBERT E. , ALLEN ALINA M. , ARMSTRONG MATTHEW J. , CONROY DAVID E. , CUTHBERTSON DANIEL J. , DUARTE-ROJO ANDRES , HALLSWORTH KATE , HICKMAN INGRID J. , KAPPUS MATTHEW R. , KEATING SHELLEY E. , PUGH CHRISTOPHER J. A. , ROTMAN YARON , SIMON TRACEY L. , VILAR-GOMEZ EDUARDO , WONG VINCENT WAI-SUN , SCHMITZ KATHRYN H. 
Published: May 2023

ABSTRACT
Although physical activity (PA) is crucial in the prevention and clinical management of nonalcoholic fatty liver disease, most individuals with this chronic disease are inactive and do not achieve recommended amounts of PA. There is a robust and consistent body of evidence highlighting the benefit of participating in regular PA, including a reduction in liver fat and improvement in body composition, cardiorespiratory fitness, vascular biology, and health-related quality of life. Importantly, the benefits of regular PA can be seen without clinically significant weight loss. At least 150 min of moderate or 75 min of vigorous intensity PA are recommended weekly for all patients with nonalcoholic fatty liver disease, including those with compensated cirrhosis. If a formal exercise training program is prescribed, aerobic exercise with the addition of resistance training is preferred. In this roundtable document, the benefits of PA are discussed, along with recommendations for 1) PA assessment and screening; 2) how best to advise, counsel, and prescribe regular PA; and 3) when to refer to an exercise specialist.
Indocyanine green fluorescence imaging may detect tumour residuals during surgery for bone and soft-tissue tumours
Authors: Wang Han , Ji Tao , Qu Huayi , Yan Taiqiang , Li Dasen , Yang Rongli , Tang Xiaodong , Guo Wei 
Published: May 2023

AimsThe aim of this study was to determine the rate of indocyanine green (ICG) staining of bone and soft-tissue tumours, as well as the stability and accuracy of ICG fluorescence imaging in detecting tumour residuals during surgery for bone and soft-tissue tumours.MethodsICG fluorescence imaging was performed during surgery in 34 patients with bone and soft-tissue tumours. ICG was administered intravenously at a dose of 2 mg/kg over a period of 60 minutes on the day prior to surgery. The tumour stain rate and signal-to-background ratio of each tumour were post hoc analyzed. After tumour resection, the tumour bed was scanned to locate sites with fluorescence residuals, which were subsequently inspected and biopsied.ResultsThe overall tumour stain rate was 88% (30/34 patients), and specific stain rates included 90% for osteosarcomas and 92% for giant cell tumours. For malignant tumours, the overall stain rate was 94%, while it was 82% for benign tumours. The ICG tumour stain was not influenced by different pathologies, such as malignant versus benign pathology, the reception (or lack thereof) of neoadjuvant chemotherapies, the length of time between drug administration and surgery, the number of doses of denosumab for patients with giant cell tumours, or the tumour response to neoadjuvant chemotherapy. The overall accuracy rate of successfully predicting tumour residuals using fluorescence was 49% (23/47 pieces of tissue). The accuracy rate after en bloc resection was significantly lower than that after piecemeal resection (16% vs 71%; p < 0.001).ConclusionA high percentage of bone and soft-tissue tumours can be stained by ICG and the tumour staining with ICG was stable. This approach can be used in both benign and malignant tumours, regardless of whether neoadjuvant chemotherapy is adopted. The technique is also useful to detect tumour residuals in the wound, especially in patients undergoing piecemeal resection.Cite this article: Bone Joint J 2023;105-B(5):551–558.
Metastasectomy of spinal lesions from thyroid carcinomas
Authors: Kato Satoshi , Demura Satoru , Yokogawa Noriaki , Shimizu Takaki , Kobayashi Motoya , Yamada Yohei , Murakami Hideki , Tsuchiya Hiroyuki 
Published: May 2023

AimsPatients with differentiated thyroid carcinomas (DTCs) have a favourable long-term survival. Spinal metastases (SMs) cause a decline in performance status (PS), directly affecting mortality and indirectly preventing the use of systemic therapies. Metastasectomy is indicated, if feasible, as it yields the best local tumour control. Our study aimed to examine the long-term clinical outcomes of metastasectomy for SMs of thyroid carcinomas.MethodsWe collected data on 22 patients with DTC (16 follicular and six papillary carcinomas) and one patient with medullary carcinoma who underwent complete surgical resection of SMs at our institution between July 1992 and July 2017, with a minimum postoperative follow-up of five years. The cancer-specific survival (CSS) from the first spinal metastasectomy to death or the last follow-up was determined using Kaplan-Meier analysis. Potential factors associated with survival were evaluated using the log-rank test. We analyzed the clinical parameters and outcome data, including pre- and postoperative disability (Eastern Cooperative Oncology Group PS 3), lung and non-spinal bone metastases, and history of radioiodine and kinase inhibitor therapies.ResultsLung and other bone metastases at the time of surgery were observed in ten and eight patients, respectively. Three patients experienced local tumour recurrences at the operated site. The five- and ten-year CSS rates in the 22 patients with DTC were 77% and 52%, respectively. Pre- and postoperative disability and operative site tumour recurrence were identified as risk factors for short postoperative survival.ConclusionMetastasectomy for resectable SM from DTC yielded favourable results and has the potential to improve survival.Cite this article: Bone Joint J 2023;105-B(5):575–582.