bluuebunny/crossref_metadata_2025_split huggingface dataset:
The effect of multidisciplinary team on survival rates of women with breast cancer: a systematic review and meta-analysis
Authors: Pangarsa Eko A. , Rizky Daniel , Tandarto Kevin , Setiawan Budi , Santosa Damai , Hadiyanto Jessica N. , Kyana Salma , Suharti Catharina 
Published: August 2023

Background:
Breast cancer is quite frequent all around the world. This disease was responsible for an estimated 2.1 million malignancies in 2022, making it the seventh-highest cause of cancer deaths globally. A multidisciplinary team (MDT) care policy was developed in the United Kingdom (UK) in 1995 to enhance the quality of care for cancer patients. The purpose of this systematic review and meta-analysis study is to assess the effects of MDT on breast cancer survival rates.

Methods:
This study was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020. Systematic search was conducted in several international databases including Google Scholar, PubMed, EBSCOhost, and Proquest from 2012 to 2022. The authors used RevMan 5.4 to do the meta-analysis of the pooled hazard ratio. Newcastle–Ottawa Scale to measure the risk of bias. Newcastle–Ottawa Scale evaluated participant selection, comparability, and reporting of results using eight subscale items. Egger’s test funnel plot was used to assess the potential publication bias for this study.

Results:
A total of 1187 studies were identified from research database. The authors found a total of six studies from six different countries (China, the UK, Taiwan, Australia, Africa, and France) included for this study. Based on the meta-analysis of the pooled hazard ratio of the included studies, the authors found that the overall effect size of the study was 0.80 (CI 95%: 0.73–0.88).

Conclusions:
Breast cancer patients who participated in well-organized MDT discussions had a greater survival rate than those who did not.
Efficacy of Arthroscopic Diskopexy on Condylar Growth in Temporomandibular Joint Anterior Disk Displacement: A Randomized Clinical Trial
Authors: Shen Pei , Bai Guo , Xie Qianyang , Fang Yiming , Pan Lulu , Geng Yang , Wu Shanshan , Li Yan , Lu Haixia , Yang Chi 
Published: August 2023

Background:
Adolescents with temporomandibular joint (TMJ) anterior disk displacement (ADD) frequently develop dentofacial deformities. It is unknown whether adjunctive arthroscopic diskopexy compared with orthodontic treatment alone increases condylar growth and then improves dentofacial deformity. This study aimed to determine whether arthroscopic diskopexy before functional appliance (joint-occlusal treatment) or single functional appliance (occlusal treatment) increases condylar growth and improves dentofacial deformity among adolescents with TMJ ADD.

Methods:
A multicenter, randomized, parallel, controlled trial was conducted in 3 centers in China. Adolescents diagnosed with TMJ ADD and dentofacial deformity were enrolled. Eligible participants were randomly assigned to a joint-occlusal group or occlusal group at a ratio of 2:1. Magnetic resonance imaging scans and cephalometric radiographs were evaluated at baseline, at 8 months, and at 14 months. The primary outcome was changes in condylar height from 14 months to baseline. Secondary outcomes were changes in skeletal position.

Results:
A total of 240 patients (14.65 ± 1.88 years of age) were randomized (joint-occlusal group, 160; occlusal group, 80). The overall difference in condylar height between groups was 3.65 mm (95% CI, 3.10 to 4.19 mm; P < 0.001). The between-group differences in condylar height on the left and right sides were 3.60 mm (95% CI, 2.92 to 4.28 mm; P < 0.001) and 3.69 mm (95% CI, 3.06 to 4.32 mm; P < 0.001), respectively. Significant between-group differences were noted in skeletal position (all P < 0.001).

Conclusion:
Joint-occlusal treatment can promote condylar growth and improve dentofacial deformity in adolescents after 14 months when compared with single occlusal treatment.

CLINICAL QUESTION/LEVEL OF EVIDENCE:
Therapeutic, I.
Myth-Busting the Zone-of-Injury Concept: A Prospective Study on the Vascular Response to High-Energy Lower Extremity Trauma
Authors: Cepas Adas , Kiiski Juha , Majava Marja , Kholová Ivana , Kaartinen Ilkka 
Published: August 2023

Background:
Although the zone-of-injury concept is widely accepted, no histologic studies of vessel wall changes causing the phenomenon have been reported. In this prospective study, the vascular response to high-energy lower extremity trauma was investigated to evaluate the validity of the zone-of-injury concept.

Methods:
The histologic appearance of arterial and venous walls in the zone of injury was studied in 19 patients (median age, 46 years; interquartile range, 29.5 to 62.5 years) who underwent osteosynthesis and free flap reconstruction after high-energy lower extremity open fracture. Vascular samples were harvested from the injured extremity, and control samples were harvested from the free flap donor site. Histologic and morphometric characteristics of the vessels were analyzed microscopically and using digital pathology QuPath software.

Results:
Vascular samples were harvested on postinjury days 1 through 11. Intimal thickness was more than 3 times greater in arteries harvested from the zone of injury than in control samples (P < 0.01), and the intima/media ratio was 2-fold that in control samples (P = 0.01). Arterial intimal fibrosis was more evident in vessels harvested from the zone of injury (P < 0.01), but medial fibrosis and medial thickness did not differ significantly between groups. Venous intimal thickening (P < 0.01) and the intima/media ratio (P = 0.02) were greater in samples from the zone of injury. Fibrosis-related changes did not differ between groups (P = 0.45).

Conclusions:
These findings support the validity of the zone-of-injury concept by providing a novel histologic basis for this phenomenon. Intimal thickening and arterial intimal fibrosis are prominent histologic features of vessels affected by major lower extremity trauma.
Can Depressive Symptomatology at Diagnosis Predict Cognitive and Functional Decline Over 1 Year in Rural Canadian Patients With Dementia?
Authors: Cai Shuang , Kirk Andrew , Karunanayake Chandima , O’Connell Megan E. , Morgan Debra 
Published: August 2023

Introduction:
Depressive symptomatology is often associated with the onset of dementia, although the exact form and directionality of this association is still unclear. The aim of this study is to investigate whether depressive symptomatology at the time of dementia diagnosis was predictive of cognitive, functional, and behavioral decline over 1 year.

Methods:
In a Rural and Remote Memory Clinic, 375 patients consecutively diagnosed with mild cognitive impairment, Alzheimer disease, or non-Alzheimer disease dementia completed the Center for Epidemiological Studies Depression Scale at first visit and 1-year follow-up to assess depressive symptomatology. The same cohort was evaluated for cognitive, functional, and behavioral decline through the completion of 5 clinical tests performed at the first visit and at 1-year follow-up.

Results:
Depressive symptomatology at time of dementia diagnosis did not predict cognitive or functional decline over 1 year, although increases in depressive symptomatology over 1 year significantly correlated with higher caregiver ratings of neuropsychiatric symptom severity and related distress over that time.

Conclusion:
Increasingly severe depressive symptomatology over 1 year correlated with greater caregiver distress. This study points the way for future studies delineating the relationship between depression, dementia progression, and caregiver distress.
A definition schema for life level and some associated models
Authors: Losonczi Attila 
Published: August 2023

AbstractWe present a mathematical definition schema for measuring life level that is to give options to describe how much a (generalized) organism is alive. It is just a definition schema, not a definition. To make it a real definition configuration is required by applications.We devote a long section to various examples where we demonstrate how a ready made definition can work and what ways it can provide reasonable values for life levels.In the second part of the paper we outline many possible ways how one can partially derive life-level values from some simpler principles using probabilistic approach and various other methods. All of those models are still going to stay on a general level however they will suggest some more specific methods.From technical point of view, we also present various kinds of operations which produce new life level functions, life level systems from already existing ones, and also highlight connections among systems / functions. Some operations also extend the usability of the original life level function, others add nice (expectable) features. We also examine the properties of such operations and the relations among them. Then we apply those techniques for some biologically meaningful extensions / restrictions of life level functions and systems.We also deal with various averages on already defined life level functions and see how they can be applied, and we also investigate metrics (biological distance functions) that are synchronized with a life level function.We also build a basic theory about measuring the vitality of sub-organisms regarding a containing (generalized) organism, and we identify some links between this notion and the life level concept.
Machine-guided design of synthetic cell type-specificcis-regulatory elements
Authors: Gosai SJ , Castro RI , Fuentes N , Butts JC , Kales S , Noche RR , Mouri K , Sabeti PC , Reilly SK , Tewhey R 
Published: August 2023

AbstractCis-regulatory elements (CREs) control gene expression, orchestrating tissue identity, developmental timing, and stimulus responses, which collectively define the thousands of unique cell types in the body. While there is great potential for strategically incorporating CREs in therapeutic or biotechnology applications that require tissue specificity, there is no guarantee that an optimal CRE for an intended purpose has arisen naturally through evolution. Here, we present a platform to engineer and validate synthetic CREs capable of driving gene expression with programmed cell type specificity. We leverage innovations in deep neural network modeling of CRE activity across three cell types, efficientin silicooptimization, and massively parallel reporter assays (MPRAs) to design and empirically test thousands of CREs. Throughin vitroandin vivovalidation, we show that synthetic sequences outperform natural sequences from the human genome in driving cell type-specific expression. Synthetic sequences leverage unique sequence syntax to promote activity in the on-target cell type and simultaneously reduce activity in off-target cells. Together, we provide a generalizable framework to prospectively engineer CREs and demonstrate the required literacy to write regulatory code that is fit-for-purposein vivoacross vertebrates.
Folded alpha helical putative new proteins fromApilactobacillus kunkeei
Authors: Ye Weihua , Behra Phani Rama Krishna , Dyrhage Karl , Seeger Christian , Joiner Joe D. , Karlsson Elin , Andersson Eva , Chi Celestine N. , Andersson Siv G. E. , Jemth Per 
Published: August 2023

ABSTRACTThe emergence of new proteins is a central question in biology. Most tertiary protein folds known to date appear to have an ancient origin, but it is clear from bioinformatic analyses that new proteins continuously emerge in all organismal groups. However, there is a paucity of experimental data on new proteins regarding their structure and biophysical properties. We performed a detailed phylogenetic analysis and identified 48 putative open reading frames in the honeybee-associated bacteriumApilactobacillus kunkeeifor which no homologs could be identified in closely-related species, suggesting that they could be relatively new on an evolutionary time scale and represent recently evolved proteins. Using circular dichroism-, fluorescence- and nuclear magnetic resonance spectroscopy we investigated five of these proteins and show that they are not intrinsically disordered, but populate alpha-helical dominated folded states with relatively low thermodynamic stability (0-3 kcal/mol). The data demonstrate that small new proteins readily adopt simple folded conformations suggesting that more complex tertiary structures can be continuously re-invented during evolution by fusion of such simple secondary structure elements. These findings have implications for the general view on protein evolution, wherede novoemergence of folded proteins may be a common event.
SUMOylation of the m6A reader YTHDF2 by PIAS1 promotes viral RNA decay to restrict EBV replication
Authors: Sugiokto Febri Gunawan , Saiada Farjana , Zhang Kun , Li Renfeng 
Published: August 2023

AbstractYTHDF2 is a member of the YTH protein family that binds to N6-methyladenosine (m6A)-modified RNA, regulating RNA stability and restricting viral replication, including Epstein-Barr virus (EBV). PIAS1 is an E3 SUMO ligase known as an EBV restriction factor, but its role in YTHDF2 SUMOylation remains unclear. In this study, we investigated the functional regulation of YTHDF2 by PIAS1. We found that PIAS1 promotes the SUMOylation of YTHDF2 at three specific lysine residues (K281, K571, and K572). Importantly, PIAS1 enhances the antiviral activity of YTHDF2, and SUMOylation-deficient YTHDF2 shows reduced anti-EBV activity. Mechanistically, YTHDF2 lacking SUMOylation exhibits reduced binding to EBV transcripts, leading to increased viral mRNA stability. Furthermore, PIAS1 mediates SUMOylation of YTHDF2’s paralogs, YTHDF1 and YTHDF3. These results collectively uncover a unique mechanism whereby YTHDF2 controls EBV replication through PIAS1-mediated SUMOylation, highlighting the significance of SUMOylation in regulating viral mRNA stability and EBV replication.ImportanceN6-methyladenosine (m6A) RNA modification pathway plays important roles in diverse cellular processes and viral life cycle. Here, we investigated the relationship between PIAS1 and the m6A reader protein YTHDF2, which is involved in regulating RNA stability by binding to m6A-modified RNA. We found that both the N-terminal and C-terminal regions of YTHDF2 interact with PIAS1. We showed that PIAS1 promotes the SUMOylation of YTHDF2 at three specific lysine residues. We also demonstrated that PIAS1 enhances the anti-Epstein-Barr virus (EBV) activity of YTHDF2. We further revealed that PIAS1 mediates the SUMOylation of other YTHDF family members, namely YTHDF1 and YTHDF3, due to their similarities with YTHDF2. These findings together illuminate an important regulatory mechanism of YTHDF2 in controlling viral RNA decay and EBV replication through PIAS1-mediated SUMOylation.
Integration of Osteoclastogenesis through addition of PBMCs in Human Osteochondral Explants culturedEx vivo
Authors: Cramer Esther E.A. , de Wildt Bregje W.M. , Hendriks Johannes G.E. , Ito Keita , Hofmann Sandra 
Published: August 2023

AbstractThe preservation of tissue specific cells in their native 3D extracellular matrix in bone explants provides a unique platform to study remodeling. Thus far, studies involving bone explant cultures showed a clear focus on achieving bone formation and neglected osteoclast activity and resorption. To simulate the homeostatic bone environmentex vivo, both key elements of bone remodeling need to be represented. This study aimed to assess and include osteoclastogenesis in human osteochondral explants through medium supplementation with RANKL and M-CSF and addition of peripheral blood mononuclear cells (PBMCs), providing osteoclast precursors.Osteochondral explants were freshly harvested from human femoral heads obtained from hip surgeries and cultured for 20 days in a two-compartment culture system. Osteochondral explants preserved viability and cellular abundance over the culture period, but histology demonstrated that resident osteoclasts were no longer present after 4 days of culture. Quantitative extracellular tartrate resistant acid phosphatase (TRAP) analysis confirmed depletion of osteoclast activity on day 4 even when stimulated with RANKL and M-CSF. Upon addition of PBMCs, a significant upregulation of TRAP activity was measured from day 10 onwards. Evaluation of bone loss trough µCT registration and measurement of extracellular cathepsin K activity revealed indications of enhanced resorption upon addition of PBMCs. Based on the results we suggest that an external source of osteoclast precursors, such as PBMCs, needs to be added in long-term bone explant cultures to maintain osteoclastic activity, and bone remodeling.Graphical abstract
MET functions in tumour progression and therapy resistance are repressed by intronic polyadenylation
Authors: Boldina Galina , Vallejos Maricarmen , Allard Delphine , Cadix Mandy , Labbé Céline , Vacher Sophie , Hemmingsson Oskar , Gestraud Pierre , Teissandier Aurélie , Martineau Sylvain , Auboeuf Didier , André Fabrice , Kamal Maud , Servant Nicolas , Bièche Ivan , Dutertre Martin , Robert Caroline , Vagner Stéphan 
Published: August 2023

AbstractIntronic polyadenylation (IPA) leads to the production of transcript isoforms with alternative last exons in thousands of mammalian genes. Widespread regulation of IPA isoforms was observed during oncogenic transformation and in tumoursversushealthy tissues, and several IPA isoforms were involved in oncogenesis. However, little is known about the potential involvement of IPA in tumour progression, such as cancer cell invasiveness and metastasis, and in resistance to anticancer therapies. Here, we show that an IPA isoform ofMET(short MET) whose production is inhibited by U1 snRNP (U1), an essential ribonucleoprotein complex that recognizes the 5’ exon-intron junction of pre-mRNA, is associated with better prognosis in breast cancer. Induction of the short MET isoform, using a steric-blocking antisense oligonucleotide targeting the U1 binding site in the vicinity of the short MET alternative polyadenylation site, antagonizes cell invasiveness. U1 blockade with an antisense oligonucleotide targeting the U1 snRNA also decreases breast cancer cell invasiveness, in both human and mouse cancer cell models, and this effect involves IPA induction inMETand several genes belonging to the RAS/RAF/MAPK signalling pathway. Finally, short MET relieves melanoma cell resistance to MAPK cascade-targeted therapyin vitroandin vivo. IPA isoform levels ofMETand a few other genes (mTOR,EGFRandCTNNA1) help predict such resistance in patients. Altogether, our findings provide evidence for a role of IPA in both cancer cell invasiveness and resistance to therapy. This suggests that IPA isoforms can be exploited as biomarkers and therapeutic targets to combat tumour progression.
Three dimensional fibrotic extracellular matrix directs microenvironment fiber remodeling by fibroblasts
Authors: Nizamoglu Mehmet , Alleblas Frederique , Koster Taco , Borghuis Theo , Vonk Judith M. , Thomas Matthew J. , White Eric S. , Watson Carolin K. , Timens Wim , Kasmi Karim C. El , Melgert Barbro N. , Heijink Irene H. , Burgess Janette K. 
Published: August 2023

AbstractIdiopathic pulmonary fibrosis (IPF), for which effective treatments are limited, results in excessive and disorganized deposition of an aberrant extracellular matrix (ECM). An altered ECM microenvironment is postulated to contribute to disease perpetuation in a feed-forward manner through inducing profibrotic behavior by lung fibroblasts, the main producers and regulators of ECM. Here, we examined this hypothesis in a 3Din vitromodel system by growing primary human lung fibroblasts in ECM-derived hydrogels from non-fibrotic (control) or IPF lung tissue. Culture of fibroblasts in fibrotic hydrogels did not trigger a change in the overall amount of collagen or glycosaminoglycans but did cause a drastic change in fiber organization compared to culture in control hydrogels. Mechanical properties of fibrotic hydrogels were modified by fibroblasts while control hydrogels were not. These results illustrate how the 3D microenvironment plays a crucial role in directing cells to exhibit pro-fibrotic responses by providing biochemical and/or biomechanical cues.
Golgi membrane proteins YIPF3 and YIPF4 regulate turnover of the Golgi apparatus through autophagy
Authors: Kitta Shinri , Kaminishi Tatsuya , Higashi Momoko , Shima Takayuki , Kosako Hidetaka , Yoshimori Tamotsu , Kuma Akiko 
Published: August 2023

AbstractThe degradation of organelles by autophagy is essential for cellular homeostasis. The Golgi apparatus has recently been demonstrated to be degraded by autophagy, but little is known about how the Golgi is recognized by the autophagosome. Using quantitative proteomic analysis and two Golgiphagy-reporter systems that we developed, we found that five-transmembrane Golgi-resident proteins, YIPF3 and YIPF4, constitute a Golgiphagy receptor. The YIPF3–YIPF4 complex interacts with LC3B, GABARAP, and GABARAPL1 via the LIR motif in YIPF3, whose stability is dependent on YIPF4. Phosphorylation of the LIR in YIPF3 seems to be required for YIPF3–ATG8 interaction. Moreover, expression of the YIPF3 LIR mutant caused an elongated Golgi morphology, indicating the importance of Golgi turnover via selective autophagy. The reporter assays that we established will pave the way for future studies to obtain deeper insights into Golgiphagy.
The catalytic rate constant ofTrichoderma longibrachiatumfamily 7 cellobiohydrolase on cellulose
Authors: Jeoh Tina 
Published: August 2023

AbstractCellobiohydrolases are considered ‘workhorse’ cellulases in the saccharification of cellulosic substrates. As solubilized cellobiose products are easily measured, cellobiohydrolases have been useful tools in studies of cellulose hydrolysis. Access to purified cellobiohydrolases with known catalytic rate constant (kcat), or the turnover rate, is particularly useful. Here, we determined the kcatof the commercially availableTrichoderma longibrachiatumCBHI at 30°C, 40°C, and 50°C to be 0.5 s-1, and 2.6 s-1, and 5.3 s-1, respectively. The energy of activation of productively boundTlCBHI was estimated to be 93 ± 17 kJ/mol.