bluuebunny/crossref_metadata_2025 huggingface dataset:
Anti-inflammatory therapy of atherosclerosis: focusing on IKKβ
Authors: Gan Jiali , Guo Lin , Zhang Xiaolu , Yu Qun , Yang Qiuyue , Zhang Yilin , Zeng Wenyun , Jiang Xijuan , Guo Maojuan
Published: February 2023

Chronic low-grade inflammation has been identified as a major contributor in the development of atherosclerosis. Nuclear Factor-κappa B (NF-κB) is a critical transcription factors family of the inflammatory pathway. As a major catalytic subunit of the IKK complex, IκB kinase β (IKKβ) drives canonical activation of NF-κB and is implicated in the link between inflammation and atherosclerosis, making it a promising therapeutic target. Various natural product derivatives, extracts, and synthetic, show anti-atherogenic potential by inhibiting IKKβ-mediated inflammation. This review focuses on the latest knowledge and current research landscape surrounding anti-atherosclerotic drugs that inhibit IKKβ. There will be more opportunities to fully understand the complex functions of IKKβ in atherogenesis and develop new effective therapies in the future.
Enhanced mild-temperature photothermal therapy by pyroptosis-boosted ATP deprivation with biodegradable nanoformulation
Authors: Liu Kaiyuan , Zhang Li , Lu Hengli , Wen Yingfei , Bi Bo , Wang Guocheng , Jiang Yingying , Zeng Leli , Zhao Jing
Published: February 2023

Background

Mild-temperature photothermal therapy (mild PTT) is a safe and promising tumor therapeutic modality by alleviating the damage of healthy tissues around the tumor due to high temperature. However, its therapeutic efficiency is easily restricted by heat shock proteins (HSPs). Thus, exploitation of innovative approaches of inhibiting HSPs to enhance mild PTT efficiency is crucial for the clinical application of PTT.

Results

Herein, an innovative strategy is reported: pyroptosis-boosted mild PTT based on a Mn-gallate nanoformulation. The nanoformulation was constructed via the coordination of gallic acid (GA) and Mn2+. It shows an acid-activated degradation and releases the Mn2+ and GA for up-regulation of reactive oxygen species (ROS), mitochondrial dysfunction and pyroptosis, which can result in cellular ATP deprivation via both the inhibiton of ATP generation and incresed ATP efflux. The reduction of ATP and accumulation of ROS provide a powerful approach for inhibiting the expression of HSPs, which enables the nanoformulation-mediated mild PTT.

Conclusions

Our in-vitro and in-vivo results demonstrate that this strategy of pyroptosis-assited PTT can achieve efficient mild PTT efficiency for osteosarcoma therapy.

Graphical Abstract
Low-intensity pulsed ultrasound triggers a beneficial neuromodulation in dementia mice with chronic cerebral hypoperfusion via activation of hippocampal Fndc5/irisin signaling
Authors: Song Degang , Chen Xiaomin , Zhou Na , Yuan Yi , Geng Shuo , Zhang Cong , Zhao Zhe , Wang Xingran , Bao Xinran , Lan Xifa , Zhang Xiangjian
Published: February 2023

Background

Exercise-related signaling Fndc5/irisin expresses in brain and acts as a crucial regulator of cognitive function, but its detailed roles in vascular dementia (VaD) are still unclear. Low intensity pulsed ultrasound (LIPUS), a novel brain stimulation approach, has been suggested as a promising treatment for dementia. Here, we investigated the activity and efficacy of Fndc5/irisin in experimental VaD, further explored whether the potential effects of LIPUS on VaD is related to Fndc5/irisin.

Methods

Mouse model of VaD was established with chronic cerebral hypoperfusion (CCH) using bilateral common carotid arteries stenosis (BCAS). Transcranial LIPUS was applied 24 h after BCAS and subsequently daily with a stimulation time of 5 min at an ultrasound pressure of 0.51 MPa for a period of 28 days. The levels of Fndc5/irisin in different brain regions, the hippocampal long-term potentiation and anti-inflammatory cytokines were investigated at day 28 after cognitive evaluation. Global Fndc5 knock-out (F5KO), forced expression or knockdown of Fndc5, and recombinant irisin application were respectively employed for mechanism exploration. The neuron dendritic spine density and astrocyte phenotype were detected in vitro.

Results

Fndc5/irisin was reduced in hippocampus of BCAS mice, forced expression hippocampal Fndc5 or bilateral intrahippocampal injection of recombinant irisin respectively improved hippocampal synaptic plasticity or inflammatory microenvironment, and then alleviated the cognitive impairments. LIPUS existed a positive efficacy in enhancing hippocampal Fndc5/irisin in BCAS mice, thus triggering a beneficial neuromodulation for VaD protection. Importantly, the neurorestorative effects of LIPUS on CCH-induced damages were totally reversed by knockdown the expression of hippocampal Fndc5 in WT mice, or in F5KO mice. Moreover, Fndc5 mediated the upregulated effects of LIPUS on spine density as well as irisin secretion of hippocampal neurons. The neuron-secreted irisin further drove reactive astrocytes to a neuroprotective phenotype.

Conclusion

LIPUS induced a neurorestorative stimulation against VaD may be through upregulation of the hippocampal Fndc5/irisin levels. Hippocampal Fndc5/irisin signaling might be a promising strategic target for VaD.
The critical role of KLF4 in regulating the activation of A1/A2 reactive astrocytes following ischemic stroke
Authors: Wang Cong , Li Longxuan
Published: February 2023

Background

We have previously demonstrated that the expression of kruppel-like transcription factor-4 (KLF-4) is upregulated in astrocytes following acute ischemic stroke (AIS) and found that KLF4 confers vascular protection against cerebral ischemic injury. However, the functional role of KLF4 in astrocyte after AIS is far from clear.

Methods

The intrinsic relationship between KLF4 and A1/A2 reactive astrocytes and the impact of astrocytic KLF4 on the activation of A1/A2 subtype astrocytes were evaluated in middle cerebral artery occlusion (MCAO) mice and oxygen–glucose deprivation and restoration (OGD/R) astrocytes.

Results

Our results demonstrated that astrocytic KLF4 expression and complement C3-positive A1 and S100 calcium binding protein A10 (S100A10)-positive A2 astrocytes were induced in the ischemic penumbra following focal cerebral ischemia, and the time course of upregulation of astrocytic KLF4 correlated closely with the activation of A2 astrocytes. The dual immunofluorescent studies displayed that in the ischemic hemisphere, where the high levels of KLF4 were expressed, there were relatively low levels of C3 expressed in the reactive astrocytes and vice versa, but KLF4 was always co-stained well with S100A10. Mechanistic analyses revealed that astrocytic KLF4 inhibited the activation of A1 astrocyte but promoted A2 astrocyte polarization after OGD/R by modulating expressions of nuclear factor-kB.

Conclusions

Astrocyte-derived KLF4 has a critical role in regulating the activation of A1/A2 reactive astrocytes following AIS.
Stereotactic body radiation therapy for prostate cancer: a study comparing 3-year genitourinary toxicity between CyberKnife and volumetric-modulated arc therapy by propensity score analysis
Authors: Ito Makoto , Yoshioka Yasuo , Takase Yuuki , Suzuki Junji , Takahashi Hironori , Minami Yoshitaka , Sakuragi Ami , Oshima Yukihiko , Okuda Takahito , Suzuki Kojiro
Published: February 2023

Background

To investigate whether the rate of stereotactic body radiation therapy-related (SBRT-related) genitourinary (GU) toxicity is lower in patients with prostate cancer treated with CyberKnife.

Methods

We retrospectively reviewed the medical records of patients with nonmetastatic prostate cancer at two institutions between 2017 and 2020. We analyzed 70 patients who were extracted by propensity score matching based on age, pre-treatment International Prostate Symptom Score (IPSS), and prostate volume. The patients were treated with SBRT, with a total dose of 36.25 Gy in five fractions over five consecutive weekdays, using CyberKnife or volumetric-modulated arc therapy (VMAT).

Results

The low-, medium-, and high-risk patients were 2, 19, and 14, respectively, in the CyberKnife group and 4, 17, and 14, respectively, in the VMAT group. The median follow-up time in both groups was 3 years. One patient with CyberKnife died of unrelated causes. No biochemical or clinical recurrence, distant metastases, or death from prostate cancer was observed.

The peak values of IPSS in the acute phase (< 3 months) were significantly lower in the CyberKnife than in the VMAT group (CyberKnife:16.2 vs VMAT:20.2, p = 0.025). In multiple regression analyses, the treatment modality (p = 0.03), age (p = 0.01), bladder medication pre-irradiation (p = 0.03), and neoadjuvant androgen deprivation therapy (p = 0.04) contributed to the peak value of the acute-phase IPSS. The incidence of treatment-related grade 2 acute GU toxicity tended to be lower in the CyberKnife than the VMAT group (CyberKnife: 22.9% vs. VMAT: 45.7%, p = 0.077). No difference was noted between the groups with regard to late IPSS or GU toxicity and gastrointestinal toxicity in all phases. Toxicities of grade ≥ 3 have not been observed to date.

Conclusions

Regardless of treatment modality, SBRT is effective in treating prostate cancer without serious toxicity. However, CyberKnife has an advantage over VMAT in terms of acute prostate symptoms.
Ten simple rules for providing bioinformatics support within a hospital
Authors: Chicco Davide , Jurman Giuseppe
Published: February 2023

Bioinformatics has become a key aspect of the biomedical research programmes of many hospitals’ scientific centres, and the establishment of bioinformatics facilities within hospitals has become a common practice worldwide. Bioinformaticians working in these facilities provide computational biology support to medical doctors and principal investigators who are daily dealing with data of patients to analyze. These bioinformatics analysts, although pivotal, usually do not receive formal training for this job. We therefore propose these ten simple rules to guide these bioinformaticians in their work: ten pieces of advice on how to provide bioinformatics support to medical doctors in hospitals. We believe these simple rules can help bioinformatics facility analysts in producing better scientific results and work in a serene and fruitful environment.
Association between serum uric acid levels and long-term mortality of metabolic dysfunction-associated fatty liver disease: a nationwide cohort study
Authors: Liu Zhening , Wang Qinqiu , Huang Hangkai , Wang Xinyu , Xu Chengfu
Published: February 2023

Background

The association between hyperuricemia and metabolic dysfunction-associated fatty liver disease (MAFLD) remains undetermined. This study aimed to examine the association of serum uric acid (SUA) levels with prevalence and long-term mortality of MAFLD in a nationally representative sample of US adults.

Methods

This analysis included 11,177 participants from the Third National Health and Nutrition Examination Survey (NHANES III, 1988–1994) with matched mortality data until 2019. We used logistic regression models to estimate the adjusted odd ratios (ORs) for factors associated with risk of MAFLD, and applied restricted cubic spline (RCS) regression to assess the non-linear associations of SUA levels with all-cause and cause-specific mortality of MAFLD. We also used Cox proportional hazards regression analysis to estimate hazard ratios (HRs) for the mortality.

Results

A higher SUA level contributed to a significant increased risk of MAFLD. every 1 mg/dL increment of SUA level was related to 17% (95% CI 9–24%) increased risk of MAFLD. Furthermore, a U-shaped association for males and a J-shaped association for females was discovered between SUA levels and all-cause mortality in participants with MAFLD. Specifically, among males, when SUA > 6.7 mg/dL, the higher SUA showed increased risk of cardio-cerebrovascular disease (CVD) mortality [HR (95% CI): 1.29 (1.05–1.58)]. As for females, only when SUA > 5.5 mg/dL, it showed a significantly positive association with risk of CVD and cancer mortality [HR (95% CI) 1.62 (1.24–2.13) and 1.95 (1.41–2.68)].

Conclusions

Elevated SUA level is significantly associated with an increased risk of MAFLD. Besides, SUA level is also a predictor of long-term mortality of MAFLD.
Graph isomorphism-based algorithm for cross-checking chemical and crystallographic descriptions
Authors: Merkys Andrius , Vaitkus Antanas , Grybauskas Algirdas , Konovalovas Aleksandras , Quirós Miguel , Gražulis Saulius
Published: February 2023

Published reports of chemical compounds often contain multiple machine-readable descriptions which may supplement each other in order to yield coherent and complete chemical representations. This publication presents a method to cross-check such descriptions using a canonical representation and isomorphism of molecular graphs. If immediate agreement between compound descriptions is not found, the algorithm derives the minimal set of simplifications required for both descriptions to arrive to a matching form (if any). The proposed algorithm is used to cross-check chemical descriptions from the Crystallography Open Database to identify coherently described entries as well as those requiring further curation.
Reconstruction of lossless molecular representations from fingerprints
Authors: Ucak Umit V. , Ashyrmamatov Islambek , Lee Juyong
Published: February 2023

The simplified molecular-input line-entry system (SMILES) is the most prevalent molecular representation used in AI-based chemical applications. However, there are innate limitations associated with the internal structure of SMILES representations. In this context, this study exploits the resolution and robustness of unique molecular representations, i.e., SMILES and SELFIES (SELF-referencIng Embedded strings), reconstructed from a set of structural fingerprints, which are proposed and used herein as vital representational tools for chemical and natural language processing (NLP) applications. This is achieved by restoring the connectivity information lost during fingerprint transformation with high accuracy. Notably, the results reveal that seemingly irreversible molecule-to-fingerprint conversion is feasible. More specifically, four structural fingerprints, extended connectivity, topological torsion, atom pairs, and atomic environments can be used as inputs and outputs of chemical NLP applications. Therefore, this comprehensive study addresses the major limitation of structural fingerprints that precludes their use in NLP models. Our findings will facilitate the development of text- or fingerprint-based chemoinformatic models for generative and translational tasks.
Insights on the effects of antimicrobial and heavy metal usage on the antimicrobial resistance profiles of pigs based on culture-independent studies
Authors: Ekhlas Daniel , Argüello Héctor , Leonard Finola C. , Manzanilla Edgar G. , Burgess Catherine M.
Published: February 2023

Antimicrobial resistance is a global threat to human, animal, and environmental health. In pig production, antimicrobials and heavy metals such as zinc oxide are commonly used for treatment and prevention of disease. Nevertheless, the effects of antimicrobials and heavy metals on the porcine resistome composition and the factors influencing this resistance profile are not fully understood. Advances in technologies to determine the presence of antimicrobial resistance genes in diverse sample types have enabled a more complete understanding of the resistome and the factors which influence its composition. The aim of this review is to provide a greater understanding of the influence of antimicrobial and heavy metal usage on the development and transmission of antimicrobial resistance on pig farms. Furthermore, this review aims to identify additional factors that can affect the porcine resistome. Relevant literature that used high-throughput sequencing or quantitative PCR methods to examine links between antimicrobial resistance and antimicrobial and heavy metal use was identified using a systematic approach with PubMed (NCBI), Scopus (Elsevier), and Web of Science (Clarivate Analytics) databases. In total, 247 unique records were found and 28 publications were identified as eligible for inclusion in this review. Based on these, there is clear evidence that antimicrobial and heavy metal use are positively linked with antimicrobial resistance in pigs. Moreover, associations of genes conferring antimicrobial resistance with mobile genetic elements, the microbiome, and the virome were reported, which were further influenced by the host, the environment, or the treatment itself.
Bacterial chondronecrosis with osteomyelitis related Enterococcus cecorum isolates are genetically distinct from the commensal population and are more virulent in an embryo mortality model
Authors: Huang Yue , Eeckhaut Venessa , Goossens Evy , Rasschaert Geertrui , Van Erum Johan , Roovers Geert , Ducatelle Richard , Antonissen Gunther , Van Immerseel Filip
Published: February 2023

Bacterial chondronecrosis with osteomyelitis (BCO) is a common cause of broiler lameness. Bacteria that are found in BCO lesions are intestinal bacteria that are proposed to have translocated through the intestinal epithelium and have spread systemically. One of the specific bacterial species frequently isolated in BCO cases is Enterococcus cecorum. In the current study, caecal isolates were obtained from birds derived from healthy flocks (12 isolates from 6 flocks), while isolates derived from caeca, colon, pericardium, caudal thoracic vertebrae, coxo-femoral joint, knee joint and intertarsal joint (hock) were obtained from broilers derived from BCO outbreaks (111 isolates from 10 flocks). Pulsed field gel electrophoresis was performed to determine similarity. Clonal E. cecorum populations were isolated from different bones/joints and pericardium from animals within the same flock, with intestinal strains carrying the same pulsotype, pointing to the intestinal origin of the systemically present bacteria. Isolates from the intestinal tract of birds from healthy flocks clustered away from the BCO strains. Isolates from the gut, bones/joints and pericardium of affected animals contained a set of genes that were absent in isolates from the gut of healthy animals, such as genes encoding for enterococcal polysaccharide antigens (epa genes), cell wall structural components and nutrient transporters. Isolates derived from the affected birds induced a significant higher mortality in the embryo mortality model as compared to the isolates from the gut of healthy birds, pointing to an increased virulence.
Capacity-building and continuing professional development in healthcare and rehabilitation in low- and middle-income countries—a scoping review protocol
Authors: Deprez Dalton , Busch Angela J. , Ramirez Paola Andrea , Pedrozo Araque Eliany , Bidonde Julia
Published: February 2023

Background

A recent world health report suggests that there is a growing rehabilitation human resource crisis. This review focuses on the capacity-building needed to meet present and future rehabilitation challenges in low- and middle-income countries (LMICs). Capacity-building is the process by which individuals and organizations obtain, improve, and retain the skills, knowledge, tools, equipment, and other resources needed to do their jobs competently. The objectives of this review are (1) to determine how capacity-building has been defined, implemented, and evaluated in LMICs and (2) to provide an overview of the effectiveness of capacity-building initiatives.

Methods

In the first of seven stages, we will refine and delimit the research. Then, we will identify relevant studies by searching five biomedical databases, two rehabilitation databases, three regional databases, and three databases of gray literature. Two independent reviewers will then select the studies using a priori selection criteria. We will exclude incomplete records, records published prior to 2000 for databases and 2010 for gray literature, and records written in languages other than English or Spanish. We will also exclude records focusing on entry-to-practice programs in academic settings. For Objective 1, using qualitative analysis software, we will extract and analyze text from included records that define or explains capacity building. For Objective 2, using an online file-sharing platform, one reviewer will extract data describing the effectiveness of capacity-building interventions and a second reviewer will verify the accuracy, with disagreements resolved by consensus. The results will be collated using tables and charts. After synthesizing the results, we will discuss the practicality and applicability of the findings with partners from Honduras and Colombia. We will use several formats and venues including presentations and publications in English and Spanish to present our results.

Discussion

To our knowledge, this will be the first attempt to systematically identify knowledge of capacity-building and rehabilitation in LMICs. This scoping review results will offer unique insights concerning the breadth and depth of literature in the area. It is anticipated that results from this scoping review will guide efforts in future capacity-building efforts in rehabilitation in LMICs.

Review registration

Busch AJ, Deprez D, Bidonde J, Ramírez PA, Araque EP. Capacity building and continuing professional development in healthcare and rehabilitation in low- and middle-income countries—a scoping review. 2021. https://doi.org/10.17605/OSF.IO/7VGXU.
Sea urchin (Diadema savignyi) extract as a novel protective agent against cisplatin induced neurotoxicity in rats
Authors: Khalil Eman A. , Swelim Hamdy , El-Tantawi Hala , Abdellatif Ahmed
Published: February 2023

Neurotoxicity is a severe side effect of platinum compounds used for cancer chemotherapy such as Cisplatin. This neurotoxicity leads to severe cognitive and nervous dysfunction, therefore, limiting the dose of Cisplatin and compromising the treatment protocol.

The present study investigates the neuroprotective effect of Sea Urchins which is a marine animal known for its rich bioactive compounds. Male Sprague Dawley rats received Cisplatin (2 mg/kg body weight) for 4 weeks, two times per week, followed by Sea Urchin extracts (50 and 100 mg/kg body weight) twice weekly for 4 weeks.

Results show that rats treated with Urchin’s extracts showed a significant improvement in the thermal (heat and cold) sensitivity compared to untreated rats. Liver enzymes Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) and Urea levels were also significantly decreased back to normal following treatment with sea urchin extracts. Brain tissue oxidative stress marker Nitric oxide (NO) and lipid peroxidation marker Malondialdehyde (MDA) increased significantly in the cisplatin-treated rats while the reduced glutathione levels (GSH) and catalase activity (CAT) showed a significant decrease. Treatment with sea Urchin extracts reversed these changes.

Histological and immunohistochemical examination of the cerebral cortex reveled degenerative changes such as karyopyknosis and shrunken necrotic ghost like neurons in the cisplatin treated groups. There was also strong positive Glial fibrillary acidic protein (GFAP) reactivity and a negative B-cell leukemia/lymphoma 2 protein (Bcl2) reaction in most apparent neurons, indicating strong apoptotic changes. Treatment with Urchin extracts reversed these changes. Quantification of cerebral cortex neurons also revealed the strong effect of the extracts. Cisplatin treated groups showed 3708 cells/ mm3 compared to 8091 cells/mm3 in the normal rats. Extract treatment increased the neuronal numbers to almost normal levels. Quantification of the Immuno-histochemical expression of GFAP showed an increase by 10-folds after cisplatin administration. A remarkable decline from the cisplatin group was seen in the extract treated groups.

In Conclusion, Sea Urchins extracts possess a strong neuroprotective activity and could provide a novel therapeutic method to prevent Cisplatin-induced neurotoxicity.
A novel methodology for writer (hand) identification: establishing Rigas Feraios wrote two important Greek documents discovered in Romania
Authors: Mamatsis Athanasios Rafail , Mamatsi Eirini , Chalatsis Constantinos , Arabadjis Dimitris , Kampouri Pandora , Papaodysseus Constantin
Published: February 2023

The main goal of the present work is to determine the hand that has written two newly discovered documents in Romania. For giving the proper answer, the authors introduced the notion of “Ideal Representative”, namely of an object that very well represents the corresponding ideal alphabet symbol that a writer had in his/her mind when writing a document by hand. Moreover, the authors have introduced a novel method, which leads to the optimal evaluation of the Ideal Representative of any alphabet symbol in association with any handwritten document. Furthermore, the authors have introduced methods for comparing these Ideal Representatives, so as a final decision about the hand that has written a document may be obtained with a highly considerable likelihood. The related analysis manifests that the two documents discovered in Romania in 1998, belong to the great personality of Rigas Feraios. The presented method of automatic handwriting Identification seems to be of general applicability.
Use of 3-dimensional printing at the point-of-care to manage a complex wound in hemifacial necrotizing fasciitis: a case report
Authors: Nyirjesy Sarah C. , Judd Ryan T. , Alfayez Yazen , Lancione Peter , Swendseid Brian , von Windheim Natalia , Nogan Stephen , Seim Nolan B. , VanKoevering Kyle K.
Published: February 2023

Background

Complex facial wounds can be difficult to stabilize due to proximity of vital structures. We present a case in which a patient-specific wound splint was manufactured using computer assisted design and three-dimensional printing at the point-of-care to allow for wound stabilization in the setting of hemifacial necrotizing fasciitis. We also describe the process and implementation of the United States Food and Drug Administration Expanded Access for Medical Devices Emergency Use mechanism.

Case presentation

A 58-year-old female presented with necrotizing fasciitis of the neck and hemiface. After multiple debridements, she remained critically ill with poor vascularity of tissue in the wound bed and no evidence of healthy granulation tissue and concern for additional breakdown towards the right orbit, mediastinum, and pretracheal soft tissues, precluding tracheostomy placement despite prolonged intubation. A negative pressure wound vacuum was considered for improved healing, but proximity to the eye raised concern for vision loss due to traction injury. As a solution, under the Food and Drug Administration’s Expanded Access for Medical Devices Emergency Use mechanism, we designed a three-dimensional printed, patient-specific silicone wound splint from a CT scan, allowing the wound vacuum to be secured to the splint rather than the eyelid.

After 5 days of splint-assisted vacuum therapy, the wound bed stabilized with no residual purulence and developed healthy granulation tissue, without injury to the eye or lower lid. With continued vacuum therapy, the wound contracted to allow for safe tracheostomy placement, ventilator liberation, oral intake, and hemifacial reconstruction with a myofascial pectoralis muscle flap and a paramedian forehead flap 1 month later. She was eventually decannulated and at six-month follow-up has excellent wound healing and periorbital function.

Conclusions

Patient-specific, three-dimensional printing is an innovative solution that can facilitate safe placement of negative pressure wound therapy adjacent to delicate structures. This report also demonstrates feasibility of point-of-care manufacturing of customized devices for optimizing complex wound management in the head and neck, and describes successful use of the United States Food and Drug Administration’s Expanded Access for Medical Devices Emergency Use mechanism.
Phylogeography and population structure of the global, wide host-range hybrid pathogen Phytophthora × cambivora
Authors: Mullett Martin S. , Van Poucke Kris , Haegeman Annelies , Focquet Fran , Cauldron Nicholas C. , Knaus Brian J. , Horta Jung Marilia , Kageyama Koji , Hieno Ayaka , Masuja Hayato , Uematsu Seiji , Webber Joan F. , Brasier Clive M. , Bakonyi József , Heungens Kurt , Grünwald Niklaus J. , Jung Thomas
Published: February 2023

Invasive, exotic plant pathogens pose a major threat to native and agricultural ecosystems. Phytophthora × cambivora is an invasive, destructive pathogen of forest and fruit trees causing severe damage worldwide to chestnuts (Castanea), apricots, peaches, plums, almonds and cherries (Prunus), apples (Malus), oaks (Quercus), and beech (Fagus). It was one of the first damaging invasive Phytophthora species to be introduced to Europe and North America, although its origin is unknown. We determined its population genetic history in Europe, North and South America, Australia and East Asia (mainly Japan) using genotyping-by-sequencing. Populations in Europe and Australia appear clonal, those in North America are highly clonal yet show some degree of sexual reproduction, and those in East Asia are partially sexual. Two clonal lineages, each of opposite mating type, and a hybrid lineage derived from these two lineages, dominated the populations in Europe and were predominantly found on fagaceous forest hosts (Castanea, Quercus, Fagus). Isolates from fruit trees (Prunus and Malus) belonged to a separate lineage found in Australia, North America, Europe and East Asia, indicating the disease on fruit trees could be caused by a distinct lineage of P. × cambivora, which may potentially be a separate sister species and has likely been moved with live plants. The highest genetic diversity was found in Japan, suggesting that East Asia is the centre of origin of the pathogen. Further surveys in unsampled, temperate regions of East Asia are needed to more precisely identify the location and range of the centre of diversity.
Role of geniculate artery embolization in the treatment of knee pain secondary to osteoarthritis
Authors: Shaker Mohamed , Mahmoud Mohamed Saied Salah , Nassar Wael A. M. , Elshimy Ahmed , Nasser Haytham Mohamed
Published: February 2023

Background

Osteoarthritis (OA) is a leading cause of chronic knee pain and disability with a reported prevalence of 25–30% of the population. Knee OA has traditionally been thought as a degenerative disease only related to chronic repetitive injury “wear and tear” mechanism, yet it is now considered as a much more complex disease of inflammatory nature induced by cytokines and inflammatory mediators through abnormal neo-vascularization (angiogenesis). The rational of geniculate artery embolization (GAE) is based on the hypothesis that suggesting a direct relationship between the abnormal angiogenesis and the chronic knee pain. As a novel treatment option based on occlusion of these abnormal neo-vessels via geniculate artery embolization, we postulated that such a mechanism will relieve pain and improve the quality of life. GAE has been previously approved as a safe and effective treatment in cases of post-knee arthroplasty hemarthrosis.

Purpose

To evaluate the feasibility, safety, and efficacy of geniculate artery embolization for OA-related knee pain.

Materials and methods

Sixteen patients with knee pain secondary to chronic OA refractory to conservative therapies for at least 6 months and not yet fit for total knee replacement were enrolled in a prospective single arm interventional study. GAE was performed using 150–300 μm microspheres. Patients were assessed and followed up using the visual analogue scale (VAS) for pain and the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) for the overall knee function at baseline and at 1 week, 1, 3, and 6 months post-embolization.

Results

A total 16 patients presented by knee pain secondary to chronic OA were enrolled. All of them showed a remarkable improvement in the VAS and WOMAC scores, with better clinical outcome after GAE. Pre- versus post-embolization ± MDs in VAS score from 8.38 ± 0.81 (baseline) to 2.88 ± 1.54 after 6 months (post-embolization) equivalent to 66.66% improvement. There was also a satisfactory improvement in the WOMAC scores, with ± MDs drop from 77.94 ± 10.62 (baseline) to 49.69 ± 15.43 (post-embolization) equivalent to 37.41% improvement. No severe or life-threatening complications were reported.

Conclusions

GAE holds promise as an effective minimally invasive procedure for the treatment of knee pain secondary to OA and could be introduced as a safe technique with no serious complications.
A rare case of pulmonary artery to left atrium fistula
Authors: Naghath Fairoze , Sathyanathan Babu Peter
Published: February 2023

Background

The first description of right pulmonary artery-to left atrium communication was done by Friedlich and coauthors in 1950. The right pulmonary artery and left atrium are directly connected by the right pulmonary artery to left atrial fistula through a thin-walled aneurysm. Here, we describe a female adult patient who underwent investigation for dyspnea and had Type 1 right pulmonary artery to left atrium connection.

Case presentation

Twenty-two-year-old female presented with history of breathlessness (New York Heart association classification grade III) for 3 years. On initial examination, her saturation was 60% with no clinical evidence of cyanosis. Initial radiographic examination and CT pulmonary angiogram revealed a dilated communication between the right inferior pulmonary artery and left atrium. The patient was then referred for cardiac MRI. The MR imaging showed the following findings: Dilated right ventricle and atrium with Ostium secundum type of atrial septal defect. Large focal outpouching was noted arising from the right inferior pulmonary artery whose inferomedial portion appeared to communicate with left atrium. The final diagnosis was right pulmonary artery to left atrial fistula-Type I with ostium secundum type atrial septal defect. Midline sternotomy was performed for ligation of this fistula with septal correction. Post surgery, patient began to improve clinically and her saturation in room air increased to 92%

Conclusions

Right pulmonary artery to left atrial fistula is different from the pulmonary AV fistula and its rarity directs the need for imaging to diagnose the condition and for management selection. The fistulous connection, which most frequently originates from the posterior wall of the descending branch of RPA and inserts into the LA, is readily seen on CT/catheter angiography. Due to the rarity of this entity and much fewer evidences in imaging, we have reported a type 1 right pulmonary artery to left atrium connection.
In vivo adenine base editing corrects newborn murine model of Hurler syndrome
Authors: Su Jing , Jin Xiu , She Kaiqin , Liu Yi , Song Li , Zhao Qinyu , Xiao Jianlu , Li Ruiting , Deng Hongxin , Lu Fang , Yang Yang
Published: February 2023

Mucopolysaccharidosis type I (MPS I) is a severe disease caused by loss-of-function mutation variants in the α-L-iduronidase (Idua) gene. In vivo genome editing represents a promising strategy to correct Idua mutations, and has the potential to permanently restore IDUA function over the lifespan of patients. Here, we used adenine base editing to directly convert A > G (TAG>TGG) in a newborn murine model harboring the Idua-W392X mutation, which recapitulates the human condition and is analogous to the highly prevalent human W402X mutation. We engineered a split-intein dual-adeno-associated virus 9 (AAV9) adenine base editor to circumvent the package size limit of AAV vectors. Intravenous injection of the AAV9-base editor system into MPS IH newborn mice led to sustained enzyme expression sufficient for correction of metabolic disease (GAGs substrate accumulation) and prevention of neurobehavioral deficits. We observed a reversion of the W392X mutation in 22.46 ± 6.74% of hepatocytes, 11.18 ± 5.25% of heart and 0.34 ± 0.12% of brain, along with decreased GAGs storage in peripheral organs (liver, spleen, lung and kidney). Collectively, these data showed the promise of a base editing approach to precisely correct a common genetic cause of MPS I in vivo and could be broadly applicable to the treatment of a wide array of monogenic diseases.
Prediction of porosity and water saturation of chalks from combined refraction seismic and reflection ground-penetrating radar measurements
Authors: Yuan Hemin , Abdu Abdurrahman Zango , Nielsen Lars
Published: February 2023

The prediction of porosity and water content of near-surface chalks is important for agricultural, environmental, hydrologic, and geologic engineering investigations. However, current methods based on laboratory measurements or crosshole ground-penetrating radar (GPR) are typically costly and applicable to only a limited area. We have combined the refraction seismic and reflection GPR data sets measured on the ground surface along a 96 m long profile line to predict the porosity and water saturation simultaneously. Using integrated rock-physics templates, we develop and apply a quantitative method that combines acoustic and electromagnetic velocities to estimate the petrophysical parameters of chalks. The seismic and GPR data are processed independently and subsequently combined to invert the porosity and water saturation. Field data tests demonstrate that the predicted results are consistent with laboratory measurements and field observations, demonstrating that the integration of seismic and GPR data facilitates efficient and reliable estimates of the porosity and saturation of chalks on scales relevant to regional field mapping. Hence, this method allows the petrophysical parameters of near-surface chalks to be evaluated efficiently at a regional scale.
Macroscopic mechanical properties of fluid-saturated sandstone at variable temperatures
Authors: Deng Wubing , Fu Li-Yun , Morozov Igor B. , Wang Zhiwei
Published: February 2023

Rocks can be viewed as composites of solid minerals with pores or cracks filled with softer material such as pore fluids, kerogen, bitumen, and other organic matter. The mechanical properties of highly viscous soft phases are highly sensitive to ambient temperatures and lead to temperature-dependent static and dynamic observations with the composite rock. However, the constituents operate by forming some effective (averaged) mechanical properties of the composite rock, and yet these averaged properties are still little known. To reveal such macroscopic temperature-dependent mechanical properties and measure their values in rock samples, a double-porosity model of porous rock with nonlinear viscosity is developed. The model is based on rigorous continuum mechanics with physically meaningful, real-valued, and time- and frequency-independent material properties and elegantly unifies the existing frequency-dependent microscopic squirt flow and mesoscopic wave-induced fluid flow models. The approach is used to accurately model the broad attenuation peaks and Young’s modulus dispersion observed in previously published laboratory experiments with glycerol-saturated Berea sandstone and invert for its mechanical properties. The observations are explained as mainly due to the temperature-dependent elastic coupling caused by non-Newtonian fluid within microcracks. Several hitherto unknown mechanical properties of the rock are constrained quantitatively: the average porosity of the microcracks, the effective high-pressure bulk modulus of the drained frame, the internal stiffness defect within the rock frame, the solid viscosities associated with bulk and shear deformations, and an exponent of nonlinearity for viscosity. These parameters constitute a Biot-consistent mechanical model of the rock, which can be used to simulate its behavior in arbitrary experimental environments. The rigorous first-principle model can be used in many applications: detailed and physically accurate interpretations of laboratory experiments, numerical wavefield simulations and seismic data inversion, reservoir characterization, geothermal exploration, thermal-enhanced oil recovery, and exploration for deep oil and gas resources in high-temperature environments.
Patient Satisfaction With Breast Cancer Care Delivery at the National Cancer Institute of Sri Lanka: Does Language Play a Role?
Authors: Thanabalasingam Susan J. , Ranawaka Sarith S. , Gunarathna Sathika S.C. , Yathev Bala , Booth Christopher M. , Seneviratne Sanjeewa , Gunasekera Sanjeeva , Wijeratne Don Thiwanka
Published: February 2023

PURPOSE

This study sought to examine whether there was an association between language barriers and patient satisfaction with breast cancer care in Sri Lanka.

METHODS

A telephone-based survey was conducted in the three official languages (Sinhala, Tamil, or English) among adult women (older than 18 years) who had been treated for breast cancer within 6-12 months of diagnosis at the National Cancer Institute of Sri Lanka. The European Organisation for Research and Treatment of Cancer Satisfaction with Cancer Care core questionnaire was adapted to assess three main domains (physicians, allied health care professionals, and the organization). All scores were linearly transformed to a 0-100 scale, and subscores for domains were summarized using means and standard deviations. These were also calculated for the Sinhalese and Tamil groups and compared.

RESULTS

The study included 72 participants (32 ethnically Tamil and 40 Sinhalese, with 100% concordance with preferred language). The most commonly reported best aspect of care (n = 25) involved affective behaviors of the physicians and nurses. Ease of access to the hospital performed poorest overall, with a mean satisfaction score of 54 (30.5). Clinic-related concerns were highlighted as the worst aspect of the care (n = 10), including long waiting times during clinic visits. Sixty-three percent of Tamil patients reported receiving none of their care in Tamil and 18% reported experiencing language barriers during their care. Tamil patients were less satisfied overall and reported lower satisfaction with care coordination ( P = .005) and higher financial burden ( P = 0.014).

CONCLUSION

Ethnically Tamil patients were significantly less satisfied than their Sinhalese counterparts and experienced more language barriers, suggesting there is a need to improve access to language-concordant care in Sri Lanka.
Waiting for Big Changes in Limited-Stage Small-Cell Lung Cancer: For Now, More of the Same
Authors: Deek Matthew P. , Haigentz Missak , Jabbour Salma K.
Published: February 2023

The Oncology Grand Rounds series is designed to place original reports published in the Journal into clinical context. A case presentation is followed by a description of diagnostic and management challenges, a review of the relevant literature, and a summary of the authors’ suggested management approaches. The goal of this series is to help readers better understand how to apply the results of key studies, including those published in Journal of Clinical Oncology , to patients seen in their own clinical practice.

Concurrent chemoradiotherapy remains central to the treatment of limited-stage small-cell lung cancer (SCLC). SCLC is one of the few tumors treated with twice-daily radiotherapy (RT) in the primary definitive setting, a regimen that was established when Intergroup 0096 demonstrated its superiority over once-daily RT. However, questions remained about the optimal chemoradiotherapy regimen given the low RT dose used in the once-daily RT arm of Intergroup 0096. CALGB 30610/RTOG 0538 and CONVERT attempted to establish whether dose-escalated once-daily RT was superior to twice-daily RT in limited-stage SCLC. Although both studies showed similar survival between treatment regimens, once-daily RT was not found to be superior to twice-daily RT, and trial design limited the ability to conclude dose-escalated once-daily RT as noninferior to twice-daily RT. Thus, twice-daily RT with concurrent chemotherapy remains a standard of care in limited-stage SCLC.
Hox11-expressing interstitial cells contribute to adult skeletal muscle at homeostasis
Authors: Flynn Corey G. K. , Ginkel Paul R. Van , Hubert Katharine A. , Guo Qingyuan , Hrycaj Steven M. , McDermott Aubrey E. , Madruga Angelo , Miller Anna P. , Wellik Deneen M.
Published: February 2023

Interstitial stromal cells play critical roles in muscle development, regeneration and repair and we have previously reported that Hoxa11 and Hoxd11 are expressed in the interstitial cells of muscles attached to the zeugopod, and are crucial for the proper embryonic patterning of these muscles. Hoxa11eGFP expression continues in a subset of muscle interstitial cells through adult stages. The induction of Hoxa11-CreERT2-mediated lineage reporting (Hoxa11iTom) at adult stages in mouse results in lineage induction only in the interstitial cells. However, Hoxa11iTom+ cells progressively contribute to muscle fibers at subsequent stages. The contribution to myofibers exceeds parallel Pax7-CreERT2-mediated lineage labeling. Nuclear-specific lineage labeling demonstrates that Hoxa11-expressing interstitial cells contribute nuclear contents to myofibers. Crucially, at no point after Hoxa11iTom induction are satellite cells lineage labeled. When examined in vitro, isolated Hoxa11iTom+ interstitial cells are not capable of forming myotubes, but Hoxa11iTom+ cells can contribute to differentiating myotubes, supporting Hox-expressing interstitial cells as a new population of muscle progenitors, but not stem cells. This work adds to a small but growing body of evidence that supports a satellite cell-independent source of muscle tissue in vivo.
Impact of an educational flyer and sensitization on performance-enhancement attitudes of bodybuilders in United Arab Emirates
Authors: Thomas Dixon , Shabeek Adhnan Abdul , Ahmed Hala , Mohammed Malak , Kawaguchi-Suzuki Marina , Anderson Ashley , Gopakumar Aji , Alhosani Reema , Khalifa Sherief , Mottram David
Published: February 2023

Background: A high proportion of bodybuilders use supplements to improve performance, with some turning to prohibited substances and methods. The attitudes of bodybuilders towards performance enhancement may be gauged through surveys such as the Performance Enhancement Attitude Scales (PEAS). Educational interventions are recommended as part of anti-doping measures. The objective of this project was to assess the impact of a pharmacy-led intervention using an antidoping educational flyer and the performance enhancement attitude scale to measure the attitude of bodybuilders in the United Arab Emirates (UAE).

Methods: The PEAS eight-item short form questionnaire was administered to male bodybuilders in the UAE. The PEAS was conducted before and after administration of an educational flyer concerning the problems associated with supplement use among bodybuilders. The Wilcoxon Signed-Rank and Kruskal Wallis tests were used for data analysis.

Results: A total of 218 bodybuilders, who reported taking dietary supplements, filled out the survey both pre and post viewing the antidoping educational flyer. A difference was observed between the full-time professional bodybuilders, students, and part-time bodybuilders with other primary occupations (p-value <0.05). In addition, PEAS score decreased among the study population for all eight PEAS items (p-value <0.05).

Conclusions: The pharmacy-led intervention using an antidoping educational flyer and sensitization by PEAS achieved more favorable scores, suggesting a significant shift of opinion toward avoiding use of performance enhancing substances among the bodybuilder study population. More research is required on sustaining the attitude and demonstrating the impact on doping behavior.