bluuebunny/crossref_metadata_2025_split huggingface dataset:
Use of bone landmarks for assessing the safety of acupuncture on the posterior midline of the neck region
Authors: Tang Zhiliang , Liu Jiao , Li Jin , Ma Chunming 
Published: April 2024

Abstract
Objective
Many acupuncture acupoints are located on the posterior midline of the neck region. The needling depth for acupuncture is important for practitioners, and an unsafe needling depth increases the possibility of damage to the spinal cord and brainstem. Can the safety of acupuncture be assessed by examining bone structures? We focused on this aim to carry out this study.

Methods
The shortest distance from the posterior border of the foramen magnum to the line joining both upper ends of the posterior border of the mastoid process was measured on 29 skulls. Distances from the posterior border of the vertebral foramen to the tip of the spinous process and posterior tubercle of the atlas were measured and evaluated from 197 dry cervical vertebrae and 31 lateral cervical radiographs of patient subjects. The anatomic relationships of the vertebral canal with the external occipital protuberance, tip of the spinous process of the axis, tip of the posterior tubercle of the atlas, and upper end of the posterior border of the mastoid process were observed and evaluated via lateral cervical radiography.

Results
The shortest distance from the foramen magnum to the line between the mastoid processes was 4.65±1.75 mm, and the distance from the superior border of the vertebral foramen of the atlas to the posterior tubercle was less than the distance from the inferior border. The distance from the superior border of the vertebral canal to the tip of the spinous process in C2-C7 was greater than the distance from the inferior border. The mean lengths of the superior border of the C2 spinous process and the inferior border of the C7 spinous process were greater than 21 mm and 31 mm, respectively. The line from the upper end of the posterior border of the mastoid process to the tip of the C2 spinous process or 10 mm deep to the tip of the C2 spinous process was posterior to the vertebral canal.

Conclusions
On the posterior midline of the neck region between the tip of spinous process of axis and external occipital protuberance, if the needle reaches the depth of the line between the upper end of posterior border of mastoid process and the tip of the spinous process of the axis, approximately 10 mm along the spinous process of the axis, the needle is in the safe region. The mean length of the C2-C7 spinous process is suitable to accommodate the needling depth of the adjacent acupoint. Bone structures can be used to effectively assess the safety of acupuncture on the posterior midline of the neck region.
Molar root canal treatment performed by undergraduate dental students; an observational study of procedural errors and student perception
Authors: El-Ma’aita Ahmad M. , Mahasneh Sari A. , Hamandi Maryam A. , Al-Rabab’ah Mohammad A. 
Published: April 2024

Abstract
Background
Molar root canal treatment (RCT) is challenging and requires training and specific skills. Rotary instrumentation (RI) reduces the time needed for instrumentation but may increase the risk of certain procedural errors. The aims of this study were to evaluate the quality of molar RCTs provided by undergraduate students, to compare the prevalence of procedural errors following manual and RI, and to assess the students’ self-perceived confidence to perform molar RCT without supervision and their preference for either manual or RI.

Methods
Molar RCTs performed by the final year students were evaluated radiographically according to predefined criteria (Appendix 1). The procedural errors, treatment details, and the students’ self-perceived confidence to perform molar RCT and their preference for either manual or RI were recorded. Descriptive statistics were performed, and the Chi-squared test was used to detect any statistically significant differences.

Results
60.4% of RCTs were insufficient. RI resulted in more sufficient treatments compared with MI (49% vs. 30.3% respectively. X2: 7.39, p = 0.007), required fewer visits to complete (2.9 vs. 4.6 respectively. X2: 67.23, p < 0.001) and was the preferred technique by 93.1% of students. The most common procedural errors were underextension of the root canal obturation (48.4%), insufficient obturation (45.5%), and improper coronal seal (35.2%) without a significant difference between the two techniques. 26.4% of the participating students reported that they did not feel confident to perform molar RCT without supervision.

Conclusion
The quality of molar RCT provided by UG students was generally insufficient. RI partially improved the technical quality of RCT compared with MI. UG students need further endodontic training and experience before they can safely and confidently practise molar RCT.
Impact of COVID-19 pandemic on depression incidence and healthcare service use among patients with depression: an interrupted time-series analysis from a 9-year population-based study
Authors: Chan Vivien Kin Yi , Chai Yi , Chan Sandra Sau Man , Luo Hao , Jit Mark , Knapp Martin , Bishai David Makram , Ni Michael Yuxuan , Wong Ian Chi Kei , Li Xue 
Published: April 2024

Abstract
Background
Most studies on the impact of the COVID-19 pandemic on depression burden focused on the earlier pandemic phase specific to lockdowns, but the longer-term impact of the pandemic is less well-studied. In this population-based cohort study, we examined the short-term and long-term impacts of COVID-19 on depression incidence and healthcare service use among patients with depression.

Methods
Using the territory-wide electronic medical records in Hong Kong, we identified all patients aged ≥ 10 years with new diagnoses of depression from 2014 to 2022. We performed an interrupted time-series (ITS) analysis to examine changes in incidence of medically attended depression before and during the pandemic. We then divided all patients into nine cohorts based on year of depression incidence and studied their initial and ongoing service use patterns until the end of 2022. We applied generalized linear modeling to compare the rates of healthcare service use in the year of diagnosis between patients newly diagnosed before and during the pandemic. A separate ITS analysis explored the pandemic impact on the ongoing service use among prevalent patients with depression.

Results
We found an immediate increase in depression incidence (RR = 1.21, 95% CI: 1.10–1.33, p < 0.001) in the population after the pandemic began with non-significant slope change, suggesting a sustained effect until the end of 2022. Subgroup analysis showed that the increases in incidence were significant among adults and the older population, but not adolescents. Depression patients newly diagnosed during the pandemic used 11% fewer resources than the pre-pandemic patients in the first diagnosis year. Pre-existing depression patients also had an immediate decrease of 16% in overall all-cause service use since the pandemic, with a positive slope change indicating a gradual rebound over a 3-year period.

Conclusions
During the pandemic, service provision for depression was suboptimal in the face of increased demand generated by the increasing depression incidence during the COVID-19 pandemic. Our findings indicate the need to improve mental health resource planning preparedness for future public health crises.
A novel variant in NSUN2 causes intellectual disability in a Chinese family
Authors: Yang Qi , Zhang Qiang , Qin Zailong , Yi Shang , Luo Jingsi 
Published: April 2024

AbstractNSUN2-intellectual disability syndrome, also known as intellectual disability type 5 (MRT5), is an autosomal recessive disorder that is characterized by intellectual disability (ID), postnatal growth retardation, dysmorphic facies, microcephaly, short stature, developmental delay, language impairment and other congenital abnormalities. The disease is caused by mutations in the NSUN2 gene, which encodes a tRNA cytosine methyltransferase that has an important role in spindle assembly during mitosis and chromosome segregation. In this study, we recruited a family that had two individuals with ID. Whole exome sequencing was performed to identify a homozygous frameshift variant (c.1171_1175delACCAT(p.Thr391fs*18*)) in NSUN2 (NM_017755.5) in the proband. The varint was confirmed as segregating in his affected brother and his parents by Sanger sequencing. The individuals that we described showed a similar dysmorphology profile to that associated with MRT5. To analyze the correlations between genotypes of NSUN2 and phenotypes of individuals with ID, we examined 17 variants and the associated phenotypes from 32 ID individuals in current and previous studies. We concluded that mutations in NSUN2 cause a wide range of phenotypic defects. Although some clinical manifestations were highly variable, the core phenotypes associated with NSUN2 mutations were dysmorphic facies, microcephaly, short stature, ID, growth restriction, language impairment, hypotonia and delayed puberty. Our study expands the genetic spectrum of NSUN2 mutations and helps to further define the genotype-phenotype correlations in MRT5.
Let it glow: genetically encoded fluorescent reporters in Plasmodium
Authors: Thiele Pia J. , Mela-Lopez Raquel , Blandin Stéphanie A. , Klug Dennis 
Published: April 2024

AbstractThe use of fluorescent proteins (FPs) in Plasmodium parasites has been key to understand the biology of this obligate intracellular protozoon. FPs like the green fluorescent protein (GFP) enabled to explore protein localization, promoter activity as well as dynamic processes like protein export and endocytosis. Furthermore, FP biosensors have provided detailed information on physiological parameters at the subcellular level, and fluorescent reporter lines greatly extended the malariology toolbox. Still, in order to achieve optimal results, it is crucial to know exactly the properties of the FP of choice and the genetic scenario in which it will be used. This review highlights advantages and disadvantages of available landing sites and promoters that have been successfully applied for the ectopic expression of FPs in Plasmodium berghei and Plasmodium falciparum. Furthermore, the properties of newly developed FPs beyond DsRed and EGFP, in the visualization of cells and cellular structures as well as in the sensing of small molecules are discussed.
Graphical Abstract
Exosomal miR-9-5p derived from iPSC-MSCs ameliorates doxorubicin-induced cardiomyopathy by inhibiting cardiomyocyte senescence
Authors: Zheng Huifeng , Liang Xiaoting , Liu Baojuan , Huang Xinran , Shen Ying , Lin Fang , Chen Jiaqi , Gao Xiaoyan , He Haiwei , Li Weifeng , Hu Bei , Li Xin , Zhang Yuelin 
Published: April 2024

AbstractDoxorubicin (DOX) is a chemotherapeutic agent widely used for tumor treatment. Nonetheless its clinical application is heavily limited by its cardiotoxicity. There is accumulated evidence that transplantation of mesenchymal stem cell-derived exosomes (MSC-EXOs) can protect against Dox-induced cardiomyopathy (DIC). This study aimed to examine the cardioprotective effects of EXOs isolated from human induced pluripotent stem cell-derived MSCs (iPSC-MSCs) against DIC and explore the potential mechanisms. EXOs were isolated from the cultural supernatant of human BM-MSCs (BM-MSC-EXOs) and iPSC-MSCs (iPSC-MSC-EXOs) by ultracentrifugation. A mouse model of DIC was induced by intraperitoneal injection of Dox followed by tail vein injection of PBS, BM-MSC-EXOs, or iPSC-MSC-EXOs. Cardiac function, cardiomyocyte senescence and mitochondrial dynamics in each group were assessed. In vitro, neonatal mouse cardiomyocytes (NMCMs) were subjected to Dox and treated with BM-MSC-EXOs or iPSC-MSC-EXOs. The mitochondrial morphology and cellular senescence of NMCMs were examined by Mitotracker staining and senescence-associated-β-galactosidase assay, respectively. Compared with BM-MSC-EXOs, mice treated with iPSC-MSC-EXOs displayed improved cardiac function and decreased cardiomyocyte mitochondrial fragmentation and senescence. In vitro, iPSC-MSC-EXOs were superior to BM-MSC-EXOs in attenuation of cardiomyocyte mitochondrial fragmentation and senescence caused by DOX. MicroRNA sequencing revealed a higher level of miR-9-5p in iPSC-MSC-EXOs than BM-MSC-EXOs. Mechanistically, iPSC-MSC-EXOs transported miR-9-5p into DOX-treated cardiomyocytes, thereby suppressing cardiomyocyte mitochondrial fragmentation and senescence via regulation of the VPO1/ERK signal pathway. These protective effects and cardioprotection against DIC were largely reversed by knockdown of miR-9-5p in iPSC-MSC-EXOs. Our results showed that miR-9-5p transferred by iPSC-MSC-EXOs protected against DIC by alleviating cardiomyocyte senescence via inhibition of the VPO1/ERK pathway. This study offers new insight into the application of iPSC-MSC-EXOs as a novel therapeutic strategy for DIC treatment.
Graphical Abstract
Pregnancy and acromegaly: clinical outcomes of retrospectively analysed data from the German acromegaly registry
Authors: Tönjes Anke , Würfel Marleen , Quinkler Marcus , Knappe Ulrich J. , Honegger Jürgen , Krause-Joppig Nina , Bacher Konrad , Deutschbein Timo , Störmann Sylvère , Schopohl Jochen , Meyhöfer Sebastian M. ,   the participants of the German Acromegaly Registry, Meyer Almuth , Gruber Matthias , Wortmann Stefanie , Klasen Christine , Karges Wolfram , Demtröder Frank , Frenzke Hanna , Laubner Katharina , Finke Reinhard 
Published: April 2024

Abstract
Context
Acromegaly is a rare disease caused by excessive growth hormone (GH) secretion, mostly induced by pituitary adenomas. The care of pregnant women with acromegaly is challenging, in part due to existing clinical data being limited and not entirely consistent with regard to potential risks for mother and child.

Objective
To retrospectively examine data on pregnancy and maternal as well as neonatal outcomes in patients with acromegaly.

Design & methods
Retrospective data analysis from 47 pregnancies of 31 women treated in centers of the German Acromegaly Registry.

Results
87.1% of the studied women underwent transsphenoidal surgery before pregnancy. In 51.1% a combination of dopamine agonists and somatostatin analogs were used before pregnancy. Three women did not receive any therapy for acromegaly. During pregnancy only 6.4% received either somatostatin analogs or dopamine agonists. In total, 70.2% of all documented pregnancies emerged spontaneously. Gestational diabetes was diagnosed in 10.6% and gravid hypertension in 6.4%. Overall, no preterm birth was detected. Indeed, 87% of acromegalic women experienced a delivery without complications.

Conclusion
Pregnancies in women with acromegaly are possible and the course of pregnancy is in general safe for mother and child both with and without specific treatment for acromegaly. The prevalence of concomitant metabolic diseases such as gestational diabetes is comparable to the prevalence in healthy pregnant women. Nevertheless, larger studies with more data in pregnant patients with acromegaly are needed to provide safe and effective care for pregnant women with this condition.
One-hole split endoscope versus unilateral biportal endoscopy for lumbar spinal stenosis: a retrospective propensity score study
Authors: Li Tusheng , Jiang Qiang , Zhong Wei , Zhu Tengyue , Lu Zhengcao , Ding Yu 
Published: April 2024

Abstract
Background
The one-hole split endoscopy (OSE) was first proposed and clinically applied in China in 2019. The aim of this study was to compare the clinical efficacy of one-hole split endoscopy (OSE) and unilateral biportal endoscopy (UBE) for treating lumbar spinal stenosis (LSS).

Methods
One hundred sixty patients with LSS who met the inclusion from November 2020 to August 2022 were analyzed and divided into OSE and UBE groups. The propensity score matching (PSM) method was used to adjust the imbalanced confounding variables between the two groups. After matching, surgical outcomes were recorded, and clinical data, including functional scores and imaging findings, were compared. Functional scores included the visual analog scale of leg pain (VAS-LP) and back pain (VAS-BP), the Japanese Orthopedic Association score (JOA), and the Oswestry Disability Index (ODI). Imaging data included dural sac cross-sectional area (DCSA), lumbar range of motion (ROM), and sagittal translation (ST).

Results
After PSM, 104 LSS patients were included in the study, and all covariates were well-balanced between the two groups. Among the matched patients, the OSE showed advantages over the UBE regarding operative time (62.42 ± 4.86 vs. 68.96 ± 4.56) and incision length (2.30 ± 0.14 vs. 2.70 ± 0.15) (P < 0.001). However, differences between the two groups in intraoperative blood loss, hospital length of stay, and complication rates were not statistically significant (P > 0.05). There was no statistically significant difference regarding VAS-BP, VAS-LP, JOA, and ODI between the two groups (P > 0.05). However, all clinical and functional scores significantly improved postoperatively (P < 0.05). Postoperative DCSA of both groups was significantly found to be improved (P < 0.05), ROM and ST remained within the normal range, and no cases of lumbar instability were recorded. According to the modified MacNab criteria, the excellent and good rates in the OSE and UBE groups were 94.23% and 90.38%, respectively, with no statistically significant difference (P = 0.713).

Conclusion
OSE is an alternative technique to UBE for the treatment of LSS, with similar satisfactory clinical outcomes, shorter operative time, and smaller incision length. Further studies are needed for long-term efficacy.
Access to care in Afghanistan after august 2021: a cross-sectional study exploring Afghans’ perspectives in 10 provinces
Authors: Valente Martina , Lamberti-Castronuovo Alessandro , Bocchini Francesca , Shafiq Yasir , Trentin Monica , Paschetto Michela , Bahdori Ghulam Ali , Khadem Jan Agha , Nadeem Mirza Sayed , Patmal Mohammand Hanif , Alizai Mohammad Tawoos , Barone-Adesi Francesco , Miccio Rossella , Ragazzoni Luca 
Published: April 2024

Abstract
Background
The Taliban takeover in August 2021 ended a decades-long conflict in Afghanistan. Yet, along with improved security, there have been collateral changes, such as the exacerbation of the economic crisis and brain drain. Although these changes have altered the lives of Afghans in many ways, it is unclear whether they have affected access to care. This study aimed to analyse Afghans’ access to care and how this access has changed after August 2021.

Methods
The study relied on the collaboration with the non-governmental organisation EMERGENCY, running a network of three hospitals and 41 First Aid Posts in 10 Afghan provinces. A 67-item questionnaire about access to care changes after August 2021 was developed and disseminated at EMERGENCY facilities. Ordinal logistic regression was used to evaluate whether access to care changes were associated with participants’ characteristics.

Results
In total, 1807 valid responses were returned. Most respondents (54.34%) reported improved security when visiting healthcare facilities, while the ability to reach facilities has remained stable for the majority of them (50.28%). Care is less affordable for the majority of respondents (45.82%). Female respondents, those who are unmarried and not engaged, and patients in the Panjshir province were less likely to perceive improvements in access to care.

Conclusions
Findings outline which dimensions of access to care need resource allocation. The inability to pay for care is the most relevant barrier to access care after August 2021 and must therefore be prioritised. Women and people from the Panjshir province may require ad hoc interventions to improve their access to care.
Clustering of HR + /HER2− breast cancer in an Asian cohort is driven by immune phenotypes
Authors: Pan Jia-Wern , Ragu Mohana , Chan Wei-Qin , Hasan Siti Norhidayu , Islam Tania , Teoh Li-Ying , Jamaris Suniza , See Mee-Hoong , Yip Cheng-Har , Rajadurai Pathmanathan , Looi Lai-Meng , Taib Nur Aishah Mohd , Rueda Oscar M. , Caldas Carlos , Chin Suet-Feung , Lim Joanna , Teo Soo-Hwang 
Published: April 2024

AbstractBreast cancer exhibits significant heterogeneity, manifesting in various subtypes that are critical in guiding treatment decisions. This study aimed to investigate the existence of distinct subtypes of breast cancer within the Asian population, by analysing the transcriptomic profiles of 934 breast cancer patients from a Malaysian cohort. Our findings reveal that the HR + /HER2− breast cancer samples display a distinct clustering pattern based on immune phenotypes, rather than conforming to the conventional luminal A-luminal B paradigm previously reported in breast cancers from women of European descent. This suggests that the activation of the immune system may play a more important role in Asian HR + /HER2− breast cancer than has been previously recognized. Analysis of somatic mutations by whole exome sequencing showed that counter-intuitively, the cluster of HR + /HER2− samples exhibiting higher immune scores was associated with lower tumour mutational burden, lower homologous recombination deficiency scores, and fewer copy number aberrations, implicating the involvement of non-canonical tumour immune pathways. Further investigations are warranted to determine the underlying mechanisms of these pathways, with the potential to develop innovative immunotherapeutic approaches tailored to this specific patient population.
Ki-67 is necessary during DNA replication for fork protection and genome stability
Authors: Stamatiou Konstantinos , Huguet Florentin , Serapinas Lukas V. , Spanos Christos , Rappsilber Juri , Vagnarelli Paola 
Published: April 2024

Abstract
Background
The proliferation antigen Ki-67 has been widely used in clinical settings for cancer staging for many years, but investigations on its biological functions have lagged. Recently, Ki-67 has been shown to regulate both the composition of the chromosome periphery and chromosome behaviour in mitosis as well as to play a role in heterochromatin organisation and gene transcription. However, how the different roles for Ki-67 across the cell cycle are regulated and coordinated remain poorly understood. The progress towards understanding Ki-67 function have been limited by the tools available to deplete the protein, coupled to its abundance and fluctuation during the cell cycle.

Results
Here, we use a doxycycline-inducible E3 ligase together with an auxin-inducible degron tag to achieve a rapid, acute and homogeneous degradation of Ki-67 in HCT116 cells. This system, coupled with APEX2 proteomics and phospho-proteomics approaches, allows us to show that Ki-67 plays a role during DNA replication. In its absence, DNA replication is severely delayed, the replication machinery is unloaded, causing DNA damage that is not sensed by the canonical pathways and dependent on HUWE1 ligase. This leads to defects in replication and sister chromatids cohesion, but it also triggers an interferon response mediated by the cGAS/STING pathway in all the cell lines tested.

Conclusions
We unveil a new function of Ki-67 in DNA replication and genome maintenance that is independent of its previously known role in mitosis and gene regulation.