Characterizing the targets of transcription regulators by aggregating ChIP-seq and perturbation expression data sets.

Mapping the gene targets of chromatin-associated transcription regulators (TRs) is a major goal of genomics research. ChIP-seq of TRs and experiments that perturb a TR and measure the differential abundance of gene transcripts are a primary means by which direct relationships are tested on a genomic scale. It has been reported that there is a poor overlap in the evidence across gene regulation strategies, emphasizing the need for integrating results from multiple experiments. Although research consortia interested in gene regulation have produced a valuable trove of high-quality data, there is an even greater volume of TR-specific data throughout the literature. In this study, we show a workflow for the identification, uniform processing, and aggregation of ChIP-seq and TR perturbation experiments for the ultimate purpose of ranking human and mouse TR-target interactions. Focusing on an initial set of eight regulators (ASCL1, HES1, MECP2, MEF2C, NEUROD1, PAX6, RUNX1, and TCF4), we identified 497 experiments suitable for analysis. We used this corpus to examine data concordance, to identify systematic patterns of the two data types, and to identify putative orthologous interactions between human and mouse. We build upon commonly used strategies to forward a procedure for aggregating and combining these two genomic methodologies, assessing these rankings against independent literature-curated evidence. Beyond a framework extensible to other TRs, our work also provides empirically ranked TR-target listings, as well as transparent experiment-level gene summaries for community use.

A randomized double-blinded trial to assess recurrence of systemic allergic reactions following COVID-19 mRNA vaccination.

BACKGROUND: Systemic allergic reactions (sARs) following coronavirus disease 2019 (COVID-19) mRNA vaccines were initially reported at a higher rate than after traditional vaccines. OBJECTIVE: We aimed to evaluate the safety of revaccination in these individuals and to interrogate mechanisms underlying these reactions. METHODS: In this randomized, double-blinded, phase 2 trial, participants aged 16 to 69 years who previously reported a convincing sAR to their first dose of COVID-19 mRNA vaccine were randomly assigned to receive a second dose of BNT162b2 (Comirnaty) vaccine and placebo on consecutive days in a blinded, 1:1 crossover fashion at the National Institutes of Health. An open-label BNT162b2 booster was offered 5 months later if the second dose did not result in severe sAR. None of the participants received the mRNA-1273 (Spikevax) vaccine during the study. The primary end point was recurrence of sAR following second dose and booster vaccination; exploratory end points included biomarker measurements. RESULTS: Of 111 screened participants, 18 were randomly assigned to receive study interventions. Eight received BNT162b2 second dose followed by placebo; 8 received placebo followed by BNT162b2 second dose; 2 withdrew before receiving any study intervention. All 16 participants received the booster dose. Following second dose and booster vaccination, sARs recurred in 2 participants (12.5%; 95% CI, 1.6 to 38.3). No sAR occurred after placebo. An anaphylaxis mimic, immunization stress-related response (ISRR), occurred more commonly than sARs following both vaccine and placebo and was associated with higher predose anxiety scores, paresthesias, and distinct vital sign and biomarker changes. CONCLUSIONS: Our findings support revaccination of individuals who report sARs to COVID-19 mRNA vaccines. Distinct clinical and laboratory features may distinguish sARs from ISRRs.

Experiment level curation of transcriptional regulatory interactions in neurodevelopment.

To facilitate the development of large-scale transcriptional regulatory networks (TRNs) that may enable in-silico analyses of disease mechanisms, a reliable catalogue of experimentally verified direct transcriptional regulatory interactions (DTRIs) is needed for training and validation. There has been a long history of using low-throughput experiments to validate single DTRIs. Therefore, we reason that a reliable set of DTRIs could be produced by curating the published literature for such evidence. In our survey of previous curation efforts, we identified the lack of details about the quantity and the types of experimental evidence to be a major gap, despite the theoretical importance of such details for the identification of bona fide DTRIs. We developed a curation protocol to inspect the published literature for support of DTRIs at the experiment level, focusing on genes important to the development of the mammalian nervous system. We sought to record three types of low-throughput experiments: Transcription factor (TF) perturbation, TF-DNA binding, and TF-reporter assays. Using this protocol, we examined a total of 1,310 papers to assemble a collection of 1,499 unique DTRIs, involving 251 TFs and 825 target genes, many of which were not reported in any other DTRI resource. The majority of DTRIs (965; 64%) were supported by two or more types of experimental evidence and 27% were supported by all three. Of the DTRIs with all three types of evidence, 170 had been tested using primary tissues or cells and 44 had been tested directly in the central nervous system. We used our resource to document research biases among reports towards a small number of well-studied TFs. To demonstrate a use case for this resource, we compared our curation to a previously published high-throughput perturbation screen and found significant enrichment of the curated targets among genes differentially expressed in the developing brain in response to Pax6 deletion. This study demonstrates a proof-of-concept for the assembly of a high resolution DTRI resource to support the development of large-scale TRNs.

Shoulder Injury Related to Vaccine Administration (SIRVA) in 16 Patients Following COVID-19 Vaccination Who Presented to Chiropractic, Orthopedic, and Physiotherapy Clinics in Hong Kong During 2021.

BACKGROUND Shoulder injury related to vaccine administration (SIRVA) occurs when an intramuscular deltoid injection is administered into the shoulder joint. This observational study describes clinical features in 16 patients with SIRVA following Coronavirus 2019 (COVID-19) vaccination who presented to chiropractic, orthopedic, and physiotherapy clinics in Hong Kong between January 1, 2021, and January 1, 2022. MATERIAL AND METHODS Adults age ≥18 with new-onset shoulder pain and imaging-confirmed shoulder pathology were retrospectively identified from 35 clinics. Patient demographics and clinical and vaccination details were extracted from the electronic medical record. Shoulder injury was determined by correlating clinical and imaging features. RESULTS Of 730 patients with shoulder pain, 16 SIRVA cases (mean age, 49±10 years, 75% female) were identified; (12/16, 75%) of patients received the Pfizer-BioNTech vaccine while (4/16, 25%) received Sinovac-CoronaVac. The most common diagnosis was adhesive capsulitis (10/16, 63%), followed by bursitis (3/16, 19%) and supraspinatus tear (3/16, 19%). Mean symptom onset was 3.5±2.5 days post-vaccination, and always occurred after the 2nd or 3rd vaccination, involving reduced shoulder range of motion (ROM). Mean baseline pain was 8.1±1 (out of 10). All patients received conservative care (eg, exercise, manual therapies). At 3-month follow-up, mean pain reduced to 2.4±1.4; all patients had normal shoulder ROM. CONCLUSIONS In the past 2 years, millions of intramuscular COVID-19 vaccinations have been administered. It is important that clinicians are aware of SIRVA as a cause of new symptoms of shoulder injury and should ask the patient about recent vaccinations, including for COVID-19.

Effectiveness of Multimodal Chiropractic Care Featuring Spinal Manipulation for Persistent Spinal Pain Syndrome Following Lumbar Spine Surgery: Retrospective Chart Review of 31 Adults in Hong Kong.

BACKGROUND The term "persistent spinal pain syndrome type 2" (PSPS-2) has been proposed by the International Association for the Study of Pain to replace the term "failed back surgery syndrome". This retrospective study aimed to evaluate effectiveness of multimodal care featuring chiropractic spinal manipulation (CSMT) in 31 adults in Hong Kong with PSPS-2. MATERIAL AND METHODS We identified new adult patients with PSPS-2 receiving CSMT from 2016 to 2018. Demographic and clinical data and baseline/follow-up numeric pain rating scale (NPRS) and Oswestry Disability Index (ODI) scores were extracted. Multiple linear regression was used to examine posttreatment NPRS and ODI reduction, with clinical variables as covariates. RESULTS Of 6589 patients with low back pain, 31 met criteria (mean age 52.2±13.7 years). Surgeries included laminectomy (81%), discectomy (13%), and fusion (6%). Mean baseline NRPS was 6.6±1.9; ODI was 43.8±15.1%. Patients received CSMT (100%), drop technique (81%), passive modalities (65%), soft tissue manipulation (13%), flexion-distraction (13%), and mechanical traction (13%). Mean posttreatment NPRS was 0.6±1.0; ODI was 2.4±3.3%. All patients had a minimum clinically important difference for NPRS (≥2/10) and ODI (≥30%). One year after treatment, 48% maintained improvement, 42% experienced recurrence; in 10%, follow-up was unavailable. Regression analysis identified younger age, shorter symptom duration, and greater baseline NPRS as predictors of NPRS reduction; and greater baseline ODI as a predictor of ODI reduction (all P<0.05). CONCLUSIONS Patients with PSPS-2 improved with multimodal care featuring CSMT, which was more effective in patients with younger age, shorter symptom duration, and higher baseline pain or disability levels.

Prevalence of Serious Pathology Among Adults with Low Back Pain Presenting for Chiropractic Care: A Retrospective Chart Review of Integrated Clinics in Hong Kong.

BACKGROUND There is a limited understanding of the frequency at which chiropractors encounter patients with serious pathology such as malignancy, fracture, and infection. This retrospective study aimed to estimate the prevalence and types of serious pathology among adults with new low back pain presenting to chiropractors in an integrated healthcare organization in Hong Kong, with the hypothesis that such pathology would be found in less than 5% of patients. MATERIAL AND METHODS We identified adults presenting to a chiropractor with new low back pain across 30 clinics with 38 chiropractors, and a subset with previously undiagnosed serious pathology from January 2020 through July 2022. Data were extracted from the electronic medical records, including messaging alerts for serious pathology, notes, radiology reports, and specialist follow-up. Descriptive statistics were utilized to analyze results. RESULTS Among the 7221 identified patients with new-onset low back pain (mean age 61.6±14.3), 35 presented with serious pathology. After excluding 54 cases not meeting inclusion criteria, the prevalence of serious pathology (95% CI) was 35/7221 (0.48%; 0.35-0.67%). Individual condition prevalence included metastasis (0.25%; 0.16-0.39%), fracture (0.12%; 0.07-0.24%), infection (0.04%; 0.01-0.12%), vascular pathology (0.03%; 0.01-0.10%), primary tumor (0.03%; 0.01-0.10%), and gastrointestinal emergency (0.01%; 0.00-0.08%). CONCLUSIONS This study found that serious pathology was uncommon among adults with new low back pain presenting for chiropractic care in Hong Kong, findings which are most consistent with previous research describing the prevalence of serious pathology among low back pain patients in primary care settings.

Drug Dosing in Patients Undergoing Therapeutic Plasma Exchange.

Therapeutic plasma exchange (TPE) is an extracorporeal process in which a large volume of whole blood is taken from the patient's vein. Plasma is then separated from the other cellular components of the blood and discarded while the remaining blood components may then be returned to the patient. Replacement fluids such as albumin or fresh-frozen plasma may or may not be used. TPE has been used clinically for the removal of pathologic targets in the plasma in a variety of conditions, such as pathogenic antibodies in autoimmune disorders. TPE is becoming more common in the neurointensive care space as autoimmunity has been shown to play an etiological role in many acute neurological disorders. It is important to note that not only does TPE removes pathologic elements from the plasma, but may also remove drugs, which may be an intended or unintended consequence. The objective of the current review is to provide an up-to-date summary of the available evidence pertaining to drug removal via TPE and provide relevant clinical suggestions where applicable. This review also aims to provide an easy-to-follow clinical tool in order to determine the possibility of a drug removal via TPE given the procedure-specific and pharmacokinetic drug properties.

Data and cooperation required for Venezuela's refugee crisis during COVID-19.

The deteriorating political and economic situation in Venezuela has ramifications far beyond the Latin American country's borders as almost five million Venezuelans fled and migrated into countries in the region due to the crisis at home. The scarcity of health services, the lack of information sharing, and the absence of reliable data in Venezuela create challenges for confronting developing health emergencies and disease outbreaks. The need for accurate data is especially dire given the current COVID-19 pandemic and evolving movement of refugees. While countries and international organizations came together to form a coordinated response to Venezuela's political and humanitarian crisis, this geopolitical progress is threatened by the rapid spread of COVID-19, and the instinct for countries to focus inwards on domestic response priorities, rather than engage in regional cooperation. It is critical that the international community set aside geopolitical differences and cooperate to seek an accurate picture of the conditions on the ground to improve the welfare of Venezuelan migrants and to provide a more robust response to the current pandemic.

Bradykinin stimulates protein kinase D-mediated colonic myofibroblast migration via cyclooxygenase-2 and heat shock protein 27.

BACKGROUND: Inflammatory bowel disease is characterized by episodic intestinal injury and repair. Myofibroblasts are gastrointestinal tract stromal cells that regulate the reparative process and are known targets of inflammatory mediators including bradykinin (BK). However, the mechanisms through which inflammation regulates myofibroblast-induced wound healing remain incompletely understood. Here, we demonstrate, for the first time, that BK stimulates myofibroblast migration through protein kinase D (PKD)-mediated activation of the cyclooxygenase-2 (COX-2) and heat shock protein 27 (Hsp27) pathways. MATERIALS AND METHODS: CCD-18Co is a human colonic myofibroblast cell line used from passages 8 to 14. An in vitro scratch assay assessed the effect of BK (100 nM) on myofibroblast migration over 24 h in the presence or absence of several inhibitors (CID755673 [10 µM] and NS398 [10 µM]). Hsp27 small interfering RNA evaluated the effect of Hsp27 on colonic myofibroblast migration. Antibodies to pPKD, pHsp27, and COX-2 evaluated expression levels by Western blot. RESULTS: BK stimulated myofibroblast migration over 24 h. BK also led to rapid and sustained phosphorylation of PKD at Ser-916, rapid phosphorylation of Hsp27 at Ser-82, and increased COX-2 expression over 4 h. BK-mediated COX-2 expression and Hsp27 phosphorylation were both inhibited by the PKD inhibitor CID755673. Similarly, BK-induced myofibroblast migration was significantly inhibited by CID755673 (P < 0.05), by the direct COX-2 inhibitor NS398 (P < 0.05), and by Hsp27 small interfering RNA (P < 0.05). CONCLUSIONS: BK stimulates myofibroblast migration through PKD-mediated activation of COX-2 and Hsp27. PKD, COX-2, and Hsp27 all appear to regulate myofibroblast cell migration, a stromal population that may play an important role in mucosal healing in the setting of inflammation.

Effects of climate change on the persistence and dispersal of foodborne bacterial pathogens in the outdoor environment: A review.

According to the Intergovernmental Panel on Climate Change (IPCC), warming of the climate system is unequivocal. Over the coming century, warming trends such as increased duration and frequency of heat waves and hot extremes are expected in some areas, as well as increased intensity of some storm systems. Climate-induced trends will impact the persistence and dispersal of foodborne pathogens in myriad ways, especially for environmentally ubiquitous and/or zoonotic microorganisms. Animal hosts of foodborne pathogens are also expected to be impacted by climate change through the introduction of increased physiological stress and, in some cases, altered geographic ranges and seasonality. This review article examines the effects of climatic factors, such as temperature, rainfall, drought and wind, on the environmental dispersal and persistence of bacterial foodborne pathogens, namely, Bacillus cereus, Brucella, Campylobacter, Clostridium, Escherichia coli, Listeria monocytogenes, Salmonella, Staphylococcus aureus, Vibrio and Yersinia enterocolitica. These relationships are then used to predict how future climatic changes will impact the activity of these microorganisms in the outdoor environment and associated food safety issues. The development of predictive models that quantify these complex relationships will also be discussed, as well as the potential impacts of climate change on transmission of foodborne disease from animal hosts.

Identification of human DNA in forensic evidence by loop-mediated isothermal amplification combined with a colorimetric gold nanoparticle hybridization probe.

A DNA test based on loop-mediated isothermal amplification (LAMP) and colorimetric gold nanoparticle (AuNP) hybridization probe to detect the presence of human DNA in forensic evidence was developed. The LAMP primer set targeted eight regions of the human cytochrome b, and its specificity was verified against the DNA of 11 animal species, which included animals closely related to humans, such as chimpanzee and orangutan. By using the AuNP probe, sequence-specific LAMP product could be detected and the test result could be visualized through the change in color. The limit of detection was demonstrated with reproducibility to be as low as 718 fg of genomic DNA, which is equivalent to approximately 100 plasmid DNA copies containing the cytochrome b DNA target region. A simple DNA extraction method for the commonly found forensic biological samples was also devised to streamline the test process. This LAMP-AuNP human DNA test showed to be a robust, specific, and cost-effective tool for the forensic identification of human specimens without requiring sophisticated laboratory instruments.

The Importance of Early Detection of Spinal Tumors Through Magnetic Resonance Imaging in Chiropractic Practices.

Primary spinal tumors such as schwannomas are uncommon causes of back pain that can be easily missed during the initial workup. Delayed diagnosis is associated with further neurological impairment. A 46-year-old man presented with a six-month history of progressive lower back pain and left leg radiculopathy. Previous treatments failed, including medications, physical therapy, acupuncture, and chiropractic manipulations. Examination revealed weakness (4/5) in left knee extension and ankle dorsiflexion. Magnetic resonance imaging (MRI) revealed a 2-cm intraspinal schwannoma at the L4 level with nerve root compression. The patient underwent laminectomy and gross total resection without any complications. The patient had near-complete symptomatic resolution six weeks postoperatively and returned to normal functioning. After four months of postoperative rehabilitation, the patient remained asymptomatic. This case reinforces the urgent need for early MRI in the presence of neurological deficits and other symptoms, despite normal radiographs. An increased suspicion of spinal tumors can prevent delays in diagnosis and minimize adverse outcomes. Multidisciplinary care optimizes the treatment of complex cases.

Dystonic Tremor as an Atypical Presentation of Cervical Radiculopathy.

Cervical radiculopathy often presents with neck pain, sensory disturbances, or motor weakness. This case report describes an atypical presentation of cervical radiculopathy manifesting as dystonic tremor and brachialgia, which has been documented only once previously. A 46-year-old, right-handed, male delivery worker presented with severe neck pain that gradually evolved into a dystonic tremor and sharp aching pain across his right shoulder. Despite medical intervention, his symptoms persisted, leading him to seek chiropractic care. Physical examination and diagnostic tests revealed degenerative osteophytes, causing bilateral foraminal impingement and narrowing. As orthopedic interventions only provide temporary relief, the patient opted for conservative chiropractic management, which led to a remarkable reduction in pain and complete resolution of the dystonic tremor and brachialgia. This case demonstrates that cervical disc prolapse may manifest with dystonic tremor due to excruciating radiculopathy. Additionally, it emphasizes the potential benefits of chiropractic care in managing such atypical presentations and underscores the need for further research on the mechanisms and management of such cases.

Metastatic Breast Cancer Presenting As Neck Pain in a Pregnant Patient.

Breast cancer metastasizing to the spine during pregnancy is a rare occurrence. A 36-year-old woman experienced persistent neck pain during the third trimester of pregnancy. The pain continued until the postpartum period, severely affecting quality of life (QOL). Physical examination revealed a restricted cervical range of motion. Spinal lesions were detected on magnetic resonance imaging. Metastatic breast cancer was confirmed through a biopsy. The patient underwent radiation therapy for spinal metastasis, chemotherapy for breast cancer, and nonsteroidal anti-inflammatory drug therapy for pain. She was referred for chiropractic care and physical rehabilitation. After six weeks of collaborative treatment, the patient experienced significant pain relief and improvement in strength, mobility, and QOL. This case report highlights the need to evaluate unexplained symptoms in pregnant and postpartum women to exclude sinister pathologies. It demonstrates the need for a multidisciplinary approach that combines oncological, chiropractic, and rehabilitative care to optimize the outcomes in patients with complex presentations.

Chiropractic Management of Lumbar Disc Herniation in a Patient With Co-existing Liver Cancer: A Case Report.

The current case report outlines the chiropractic management of a 30-year-old male construction worker who presented with symptoms of lumbar disc herniation with co-existing stage IV liver cancer. The patient reported experiencing substantial lower back pain and decreased sensation in his right leg following a fall at work, impacting his mobility and quality of life. The complexity of this case is underscored by the challenge of differentiating between pain due to metastatic disease and that related to the fall. The chiropractic treatment plan included gentle joint mobilization, instrument-assisted soft tissue mobilization, and low-impact exercises tailored to the patient's overall health status. The treatment protocol markedly improved pain levels, range of motion, and overall quality of life. This case highlights the potential role of chiropractic care in managing complex cases of lumbar disc herniation, even in the presence of severe illnesses such as liver cancer. This study provides valuable insights into the importance of personalized and adaptable treatment strategies in managing such cases, contributing a unique perspective to the scientific literature.

Conservative Management of Trigeminal Neuralgia and Degenerative Cervical Myelopathy: A Case Report.

It is hypothesized that degenerative cervical myelopathy (DCM) may induce or exacerbate trigeminal neuralgia (TN) through mechanisms such as direct compression of the spinal trigeminal tract, inflammation, or vascular issues, leading to ischemia within cervical segments C3-C4, where the spinal trigeminal nucleus extends. Here, we report the potential therapeutic impact of chiropractic treatment in a 55-year-old female with TN resistance to medical therapy and DCM. The patient received targeted chiropractic care, consisting of high-velocity, low-amplitude (HVLA) spinal manipulation of the C3-C7 and T1-T4 vertebral segments to address joint dysfunction, coupled with intermittent mechanical cervical traction for 20-minute sessions, and focused radial shockwave therapy aimed at myofascial trigger points within the trapezius and levator scapulae muscles. After initiating the chiropractic care plan, the patient experienced a significant reduction in the frequency and severity of TN pain, which persisted throughout the treatment period. Notably, this alleviation in symptoms was maintained at the six-month follow-up, suggesting a sustained therapeutic effect rather than a transient improvement. The lasting nature of the pain reduction provides a compelling argument for the long-term benefits of chiropractic intervention in the management of TN, particularly in cases with concurrent DCM.

Multimodal Management of Coexisting Atlantoaxial Subluxation and Spinal Stenosis in an Older Adult: A Case Report and Literature Review.

This case report investigates the diagnostic and therapeutic challenges caused by the coexistence of atlantoaxial subluxation and spinal stenosis in a 70-year-old male patient with chronic progressive numbness in both hands. A detailed assessment showed that the patient's symptoms were primarily caused by spinal stenosis, not atlantoaxial subluxation. Considering the patient's age and preference for nonsurgical treatment, a conservative chiropractic care plan was implemented, significantly improving his symptoms and quality of life. This case highlights the potential benefit of conservative chiropractic care in managing such complex cases, emphasizes the need for meticulous diagnosis, and requires further research to validate these findings and develop comprehensive management guidelines.

Exploring Chiropractic Healthcare in Hong Kong: Sick Leave Certification Dilemma.

Objective This study aims to investigate the characteristics of chiropractic patients in Hong Kong, their experiences with chiropractic care, and their perspectives on chiropractors' authority over sick leave certificates. Method A cross-sectional survey was conducted among individuals receiving chiropractic treatment in Hong Kong. Data were collected through an online survey from May 11 to August 8, 2023, and descriptive analysis was employed to examine patient demographics, treatment effectiveness, and views on chiropractic sick leave authorization. A total of 522 valid responses were received. Result Among respondents, back pain was the primary reason for seeking chiropractic care, with many experiencing rapid relief and high satisfaction. However, many patients initially consulted other healthcare professionals, indicating potential integration challenges. Lengthy orthopedic wait times in Hong Kong highlight the need for chiropractic care. Concerns arose over chiropractors' inability to issue sick leave certificates, impacting patient convenience, treatment effectiveness, finances, and emotional well-being. Allowing chiropractors to authorize sick leave, with proper regulation, could address these issues. Conclusion In conclusion, this study underscores chiropractic care's potential in Hong Kong's healthcare system and suggests that recognizing chiropractors' role in sick leave authorization can enhance comprehensive patient care.

Remission of cervicogenic dysphagia associated with biomechanical dysfunction following chiropractic therapy.

Cervicogenic dysphagia is a complex condition that can arise from biomechanical dysfunction in the cervical spine. Conventional treatment outcomes are not always guaranteed. Chiropractic treatment is considered an alternative treatment for dysphagia, yet there is a lack of evidence supporting its effectiveness. We present the case of a 48-year-old male who had difficulty swallowing for eight months. He had a feeling of food stuck in his throat when eating hard food but without any pain when swallowing, and eventually, he could not swallow any dry food. He was diagnosed with dysphagia associated with an anxiety disorder and was treated with medication, but there was no improvement in his condition. A full-spine radiograph revealed biomechanical dysfunction, including reduced cervical lordosis and levoscoliosis of the upper thoracic spine. After nine months of conventional physiotherapy, the patient completely recovered from his symptoms, with significantly improved biomechanical parameters. This study highlights the potential mechanism of cervicogenic dysphagia and the effect of chiropractic treatment in managing it. Applying chiropractic treatment, including spinal manipulative therapy, instrument-assisted soft tissue manipulation, and mechanical traction, might bring a positive outcome for dysphagia patients with careful consideration.