A unified atlas of CD8 T cell dysfunctional states in cancer and infection.

CD8 T cells play an essential role in defense against viral and bacterial infections and in tumor immunity. Deciphering T cell loss of functionality is complicated by the conspicuous heterogeneity of CD8 T cell states described across experimental and clinical settings. By carrying out a unified analysis of over 300 assay for transposase-accessible chromatin sequencing (ATAC-seq) and RNA sequencing (RNA-seq) experiments from 12 studies of CD8 T cells in cancer and infection, we defined a shared differentiation trajectory toward dysfunction and its underlying transcriptional drivers and revealed a universal early bifurcation of functional and dysfunctional T cell states across models. Experimental dissection of acute and chronic viral infection using single-cell ATAC (scATAC)-seq and allele-specific single-cell RNA (scRNA)-seq identified state-specific drivers and captured the emergence of similar TCF1+ progenitor-like populations at an early branch point, at which functional and dysfunctional T cells diverge. Our atlas of CD8 T cell states will facilitate mechanistic studies of T cell immunity and translational efforts.

Chromatin interaction-aware gene regulatory modeling with graph attention networks.

Linking distal enhancers to genes and modeling their impact on target gene expression are longstanding unresolved problems in regulatory genomics and critical for interpreting noncoding genetic variation. Here, we present a new deep learning approach called GraphReg that exploits 3D interactions from chromosome conformation capture assays to predict gene expression from 1D epigenomic data or genomic DNA sequence. By using graph attention networks to exploit the connectivity of distal elements up to 2 Mb away in the genome, GraphReg more faithfully models gene regulation and more accurately predicts gene expression levels than the state-of-the-art deep learning methods for this task. Feature attribution used with GraphReg accurately identifies functional enhancers of genes, as validated by CRISPRi-FlowFISH and TAP-seq assays, outperforming both convolutional neural networks (CNNs) and the recently proposed activity-by-contact model. Sequence-based GraphReg also accurately predicts direct transcription factor (TF) targets as validated by CRISPRi TF knockout experiments via in silico ablation of TF binding motifs. GraphReg therefore represents an important advance in modeling the regulatory impact of epigenomic and sequence elements.

Radiotherapy for benign diseases in Turkey: a patterns of care survey of the Turkish Society for Radiation Oncology (TROD 05-002).

PURPOSE: We aimed to investigate the patterns of radiotherapy (RT) care in cases of benign diseases in Turkey. METHODS: A questionnaire survey was sent to all radiation oncology (RO) departments in Turkey. The number of patients treated for benign disease between 2015 and 2020 was requested. A list of benign conditions was given, and information on the number of patients per disease, single and total doses prescribed, weekly fractions, radiation type, energy, and device was requested. RESULTS: Of the 138 RO departments, 29 (21%) responded. The data received concerned 15 (52%) university, 10 (34%) public, and four (14%) private hospitals. A total of 130,846 patients were treated with RT in these departments. Of these patients, 6346 (4.85%) were treated for benign conditions. The most common benign diseases treated with RT were meningioma (35%), plantar fasciitis (19%), schwannoma (16%), arteriovenous malformation (11%), and pituitary adenoma (7%). Most centers performed RT for paraganglioma, heterotopic ossification, vertebral hemangioma, and Graves' ophthalmopathy, but none treated arthrosis. Wide variations were observed across the departments. Radiosurgery for intracranial pathologies was performed intensively in four centers. By contrast, RT for plantar fasciitis was predominantly treated in five centers, one of which had more than 1000 patients. CONCLUSION: The ratio of patients who underwent RT for benign diseases in Turkey among all patients who underwent RT was 4.85%. The common pattern of RT in 72% of patients was radiosurgery for intracranial benign diseases, followed by low-dose RT for plantar fasciitis in 19%.

Local anesthetics allergy in children: Evaluation of diagnostic tests with Real-Life data.

BACKGROUND: Local anesthetic (LA) drugs are commonly used in clinical practice to provide effective analgesia, including in dentistry and minor surgical procedures. The perception of a high risk of allergy in daily applications leads to the referral of atopic patients and those with other drug allergies to allergy clinics for the evaluation of allergic reactions to LA. The aim of this study was to determine who should be referred to the allergy clinic for LA allergy testing, assess the frequency of LA allergy in pediatric patients, and identify the negative predictive value of skin tests in diagnosis. METHODS: January 2017-July 2023, the clinical and laboratory data, as well as the results of drug allergy tests, of patients referred to our pediatric allergy clinic by dentists and physicians performing minor surgical procedures with suspected LA allergy were retrospectively evaluated. RESULTS: Our study included a total of 153 patients, comprising 84 girls (54.9%) and 69 boys (45.1%), with a mean age of 8.9 (±3.3) years. The most common reason for referral was a history of non-LA drug allergies (n = 66, 43.2%), followed by asthma (n = 25, 16.3%). Hypersensitivity reactions (HRs) with LA were most commonly associated with articaine (n = 7, 4.8%), followed by lidocaine (n = 6, 4.1%). When intradermal tests were evaluated, 17 patients (11.1%) had a positive test result. The positivity for lidocaine was 70.6% (n = 12), and prilocaine was 29.4% (n = 5). Subcutaneous provocation was administered to 109 patients (71.2%), and one patient exhibited local erythema and swelling with prilocaine. CONCLUSION: Although LA allergy is a rare occurrence, consultations of this nature are frequently requested from allergy clinics in real life. Considering the negative predictive value of skin tests performed with LA drugs, the reaction rate appears to be low in patients with atopy or other drug allergies. It is crucial for all relevant healthcare professionals to be knowledgeable about the appropriate approach to suspected LA allergies to avoid unnecessary tests. To the best of our knowledge, our study is the most comprehensive work in the literature that evaluates the results of diagnostic tests in children referred with a suspicion of LA allergy.

Evaluation of neurocognitive and social developments after craniosynostosis surgery.

OBJECTIVE: The study focused on assessing the potential neurocognitive and social developmental issues in children with non-syndromic craniosynostosis (NSC) who received optimal surgical treatment. The primary objective was to determine whether NSC, even after optimal surgical treatment, could have negative effects on brain development. METHODS: The study included a total of 73 pediatric patients aged between 2 and 6 years who had previously undergone surgery for NSC at the Gazi University Faculty of Medicine, Department of Neurosurgery. These patients were carefully matched with 107 healthy children who visited the outpatient clinic of the same department in terms of sociodemographic characteristics such as age, gender, and social status. To assess the neurocognitive and social development of the participants, the child psychologist administered a developmental scale to the child and his/her family via video conference. This scale was adapted from the Bayley-III Infant and Child Development Scale by the Gazi University Faculty of Medicine, Division of Pediatric Neurology. RESULTS: The study found no social or gross motor developmental issues in patients who had undergone optimal surgical treatment for NSC. However, the risk of fine motor developmental deficiencies was 4.79 times higher than that of the normal population, and the risk of language developmental deficiencies was 5.75 times higher than that of the normal population. CONCLUSIONS: Despite timely treatment of NSC, long-term neurocognitive and social development issues may arise in affected children. Therefore, it is crucial to monitor these patients after completing surgical treatment and thoroughly examine their development using a multidisciplinary approach.

Experiences of Nurses Providing Care to Individuals in Earthquake-Affected Areas of Eastern Turkey: A Phenomenological Study.

PURPOSE: The aim of this study is to examine the experiences of nurses who provide care to individuals in earthquake-affected areas of eastern Turkey. DESIGN: A phenomenological design from qualitative research methods was utilized in this study. METHODS: The study was conducted between May 29, 2023, and August 15, 2023, with 11 nurses working in the western region of Turkey's provinces through one-on-one semi-structured interviews. The interviews were conducted online and recorded on video. Content analysis was performed using the MAXQDA software package. FINDINGS: Themes and sub-themes were identified from the expressions of nurses in line with research findings. Accordingly, 5 themes were determined for nurses providing care to individuals in the earthquake. zone: "challenges they face,""emotions they felt,""coping methods,""knowledge and skills"and "effects of earthquake". CONCLUSION: The results obtained from this study demonstrated that nurses experienced difficulties due to environmental (hygiene, cold weather, shelter) and work-related (lack of coordination, psychosocial issues) conditions during the earthquake event. While providing care to individuals in earthquake-affected areas of eastern Turkey, nurses reported feelings of sadness, inadequacy, anxiety, and fear. They employed coping methods such as talking to family/friends, attempting not to dwell on thoughts, and turning to religious practices to manage these negative emotions. Nurses emphasized the necessity of having professional knowledge and crisis management skills to care for individuals during the earthquake period. In accordance with the findings of the research, it is recommended that nurses are provided with realistic training through simulations and drills in disaster management, as well as psychological support interventions.

Bisphenol derivatives in cord blood and association between thyroid hormones and potential exposure sources.

Endocrine-disrupting environmental chemicals are a public health concern, particularly fetal exposure to Bisphenol derivatives. This study aimed to assess fetal exposure to Bisphenol derivatives (BPA, BPF, and BPS) by measuring their levels in cord blood and investigating their association with plastic material used in daily life as well as cord blood TSH and free L-thyroxine (fT4) levels. In this descriptive study, a questionnaire with a face-to-face interview was administered before birth, and cord blood samples were taken immediately after delivery. The mean levels of BPA, BPF, TSH, and fT4 were measured as 10.69 ± 2.39 ng/ml, 3.80 ± 0.58 ng/ml; 2.36 ± 0.23 µIU/ml, and 14.18 ± 0.53 pg/ml, respectively, in a total of 104 cord blood samples. All BPS levels remained below the detection limit. Linear regression analysis revealed a positive association between birth weight and cord blood BPA concentration (ß = 0.26; p = 0.02). Further research on maternal exposure during the fetal and neonatal period is critical for public health.

Incontinence-Associated Dermatitis: Prevalence in Intensive Care Units and Knowledge, Attitudes, and Practices of Nurses.

BACKGROUND: Incontinence-associated dermatitis (IAD) is a major concern among hospitals, especially in intensive care units (ICUs). PURPOSE: To describe ICU nurses' knowledge, attitudes, and practices of IAD and to examine the relationships with IAD prevalence in the ICU setting. METHODS: A descriptive correlational design was used including the Knowledge, Attitudes and Practices of Incontinence-Associated Dermatitis Questionnaire and 1-month IAD prevalence data. RESULTS: The prevalence of IAD in ICUs was 6.89%. A positive correlation was found between IAD prevalence and nurses' IAD knowledge and attitudes. Nurses working in the ICU for more than 7 years, caring for patients at high risk for or having IAD, and thinking IAD-related nursing practices were sufficient had significantly higher IAD knowledge, attitudes, and practices. CONCLUSIONS: Findings indicate that ICU nurses learned about IAD through clinical experience and have inadequate training on IAD. A standardized evidence-based care protocol for IAD should be developed.

Selective local postoperative radiotherapy for T3-T4 N0 laryngeal cancer.

PURPOSE: We aimed to investigate the appropriate postoperative radiotherapy dose and selective volume in T3-4 N0 laryngeal cancer patients treated with either total or partial laryngectomy. METHODS: Patients who received radiotherapy for locally advanced (T3-T4) and pathologic node-negative (N0) squamous cell laryngeal cancer were retrospectively evaluated. Radiotherapy was applied to median 60 Gy (range 54-60 Gy) as selective local radiotherapy (±stoma). The local treatment areas included postoperative bed + laryngeal area for patients with a partial laryngectomy, and the postoperative bed only for patients with total laryngectomy. RESULTS: The median follow-up time was 59 months and 52 patients were included. The 2­year, 5­year, and 8­year locoregional recurrence controls (LRC) were 95.6%. The 2­year and 5­year OS rates were 93.8% and 78.9%, respectively. The 5­year OS for age < 60 years was 95.8%, for above 60 years 56.5%. CONCLUSION: Our data suggest that local selective irradiation to the postoperative bed + stoma is enough in patients with T3-4 N0 laryngeal cancer without applying elective nodal irradiation.

Recurrence patterns of pancreatic cancer treated with adjuvant intensity modulated radiotherapy.

Background: The aim of this study was to investigate the recurrence patterns in pancreatic cancer patients treated with adjuvant intensity modulated radiotherapy (IMRT) and to correlate the sites of locoregional recurrence with radiotherapy target volumes. Materials and methods: Thirty-eight patients who had undergone resection and adjuvant chemoradiation for pancreatic cancer were evaluated. Radiotherapy (RT) was started after 1-3 cycles of adjuvant chemotherapy (CHT). Clinical target volume (CTV) was contoured according to the RTOG guideline. All patients were treated with IMRT with a dose of 45-50.4 Gy. Computerized tomography (CT) images at the time of recurrence were correlated with radiotherapy plans. Locoregional recurrences were classified as in-field, out-field and marginal. Results: Median overall survival (OS) was 19 months. One- and 2-year OS rates were 73.6% and 37.1%, respectively. Locoregional recurrence and distant metastases were observed in 11 (28.9%) and 23 (60.5%) patients, respectively. For the 11 locoregional recurrences, 7 were in-field, 1 was marginal, and 3 were out-of-field. One patient had isolated local, 2 patients had isolated regional and 15 (57.6%) patients had only distant failures. The first presentations of failures were mostly distant (58%). On multivariate analysis, tumor size ≥ 3 cm (p = 0.011) and positive vascular invasion (p = 0.014) predicted for worse OS rate. Conclusions: The majority of locoregional recurrences were in the radiation field among pancreatic cancer patients treated with postoperative IMRT. However, failures were predominantly distant, and improvement of systemic control may be of particular interest.

First report of Nitzschia navis-varingica in the Mediterranean Sea and growth stimulatory effects of Nitzschia navis-varingica, Chrysochromulina alifera and Heterocapsa pygmaea on different mammalian cell types.

A benthic diatom, Nitzschia navis-varingica was found for the first time in the Mediterranean Sea. Effects of this diatom species together with the haptophyte Chrysochromulina alifera and the dinoflagellate Heterocapsa pygmaea isolated from the northeastern Mediterranean Sea coast on prostate, breast cancer and fibroblast cell lines were investigated. Algal extracts did not exert any toxic effect on these cell lines and it had growth stimulatory impact on the cells without discrimination of cell type. Our results suggest potential use of these algal extracts in tissue repair and cell growth boosting additive in the diet of humans as well as animals. Moreover, these algal extracts have potential to be used as natural resource in the skin vitalizing creams of cosmetics industry and as wound healing agents in the atopic drugs.

Adaptive Evolution of Thermotoga maritima Reveals Plasticity of the ABC Transporter Network.

Thermotoga maritima is a hyperthermophilic anaerobe that utilizes a vast network of ABC transporters to efficiently metabolize a variety of carbon sources to produce hydrogen. For unknown reasons, this organism does not metabolize glucose as readily as it does glucose di- and polysaccharides. The leading hypothesis implicates the thermolability of glucose at the physiological temperatures at which T. maritima lives. After a 25-day laboratory evolution, phenotypes were observed with growth rates up to 1.4 times higher than and glucose utilization rates exceeding 50% those of the wild type. Genome resequencing revealed mutations in evolved cultures related to glucose-responsive ABC transporters. The native glucose ABC transporter, GluEFK, has more abundant transcripts either as a result of gene duplication-amplification or through mutations to the operator sequence regulating this operon. Conversely, BglEFGKL, a transporter of beta-glucosides, is substantially downregulated due to a nonsense mutation to the solute binding protein or due to a deletion of the upstream promoter. Analysis of the ABC2 uptake porter families for carbohydrate and peptide transport revealed that the solute binding protein, often among the transcripts detected at the highest levels, is predominantly downregulated in the evolved cultures, while the membrane-spanning domain and nucleotide binding components are less varied. Similar trends were observed in evolved strains grown on glycerol, a substrate that is not dependent on ABC transporters. Therefore, improved growth on glucose is achieved through mutations favoring GluEFK expression over BglEFGKL, and in lieu of carbon catabolite repression, the ABC transporter network is modulated to achieve improved growth fitness.

Relationship between maternal antenatal attachment and traumatic childbirth perception among pregnant women.

OBJECTIVE: To examine the relationship between the perception of traumatic birth and maternal attachment in pregnant women. METHODS: This descriptive and correlational study recruited 370 pregnant women who applied for an antenatal visit to outpatient clinics of a state hospital. The data were collected using a Personal Information Form, Maternal Antenatal Attachment Scale (MAAS), and Traumatic Birth Perception Scale (TBPS). Data were collected using the face-to-face method. The study was reported according to the STROBE. RESULTS: The mean total score of MAAS was 75.71 ± 7.72 and the mean TBPS score was 73.21 ± 28.34. Normal birth pain was perceived as "severe" by 38.3% of pregnant women and as "very severe" by 46.1%. It was determined that 29.2% of pregnant women had a "high" level of traumatic birth perception and 14.5% had a "very high" level. A negative correlation was found between the mean scores of MAAS and TBPS of pregnant women. The trimester of pregnancy, listening to the birth story, planned pregnancy, and traumatic birth perception, was a significant predictor of maternal antenatal attachment. CONCLUSION: As the maternal antenatal attachment levels of pregnant women increased, their perceptions of traumatic birth decreased.

In vitro 5-fluorouracil release properties investigation from pH sensitive sodium alginate coated and uncoated methyl cellulose/chitosan microspheres.

5-Fluorouracil (5-FU) has been in clinical practice for decades one of the oldest chemotherapy agents. However, intravenous administration of 5-FU requires the development of an oral controlled delivery system for improved patient compliances. For this purpose, 5-FU loaded and sodium alginate (NaAlg) coated and uncoated methyl cellulose (MC)/chitosan (CS) microspheres were prepared by emulsion crosslinking method using a mixture of water and oil. Firstly, MC/CS microspheres were prepared and then coated with NaAlg. The prepared microspheres were characterized by optical microscopy, Fourier transform infrared spectroscopy (FTIR), and differential scanning calorimetry (DSC). Microspheres were also characterized by equilibrium swelling values and drug release profiles. The in vitro drug release studies were carried out with three pH values 1.2, 6.8, and 7.4, respectively, each for 2 h. It was determined that coating the microspheres with NaAlg provides more controlled drug release, especially at pH 1.2. The effects of the preparation conditions, such as coating time, MC/CS ratio, NaAlg concentration, and crosslinker concentration on the 5-FU release were investigated.

Comparison of Cost Analysis in Patients with Tetrahydrobiopterin-Responsive and Non-Responsive Phenylketonuria in Turkey.

Phenylketonuria is an inherited metabolic disorder that leads to neurobehavioral dysfunction. The main treatment is a low-phenylalanine diet and/or the cofactor tetrahydrobiopterin. Regular outpatient follow-up care and measurement of the phenylalanine levels in the blood are required. We aimed to analyze the economic burden of phenylketonuria on families and the state. The patients with phenylketonuria were divided into three groups according to their treatment: a low-phenylalanine diet group (n = 50), a tetrahydrobiopterin group (n = 44), and a group taking tetrahydrobiopterin together with the diet (n = 25). A comparative cost analysis was carried out. The annual economic burden to the state was calculated to average EUR 18,801 ± 15,345 and was lowest in the diet group, then in the tetrahydrobiopterin group, and highest in the tetrahydrobiopterin + diet group (p < 0.001). Out-of-pocket costs amounted to EUR 1531 ± 1173 per year, and indirect losses averaged EUR 2125 ± 1930 per year for all families. The economic loss was significantly lower in the families taking tetrahydrobiopterin than in the other groups (p = 0.001). The combined use of medical nutrition and BH4 treatments has been shown to increase the economic burden on the state. Reimbursing low-protein products and increasing the number of patients eligible for financial allowances may reduce the economic burden on families.

Beyond human in neurosurgical exams: ChatGPT's success in the Turkish neurosurgical society proficiency board exams.

Chat Generative Pre-Trained Transformer (ChatGPT) is a sophisticated natural language model that employs advanced deep learning techniques and is trained on extensive datasets to produce responses akin to human conversation for user inputs. In this study, ChatGPT's success in the Turkish Neurosurgical Society Proficiency Board Exams (TNSPBE) is compared to the actual candidates who took the exam, along with identifying the types of questions it answered incorrectly, assessing the quality of its responses, and evaluating its performance based on the difficulty level of the questions. Scores of all 260 candidates were recalculated according to the exams they took and included questions in those exams for ranking purposes of this study. The average score of the candidates for a total of 523 questions is 62.02 ± 0.61 compared to ChatGPT, which was 78.77. We have concluded that in addition to ChatGPT's higher response rate, there was also a correlation with the increase in clarity regardless of the difficulty level of the questions with Clarity 1.5, 2.0, 2.5, and 3.0. In the participants, however, there is no such increase in parallel with the increase in clarity.

The Impact of the Pandemic on Cat and Dog Allergies.

Objectives: The impact of the COVID-19 pandemic on allergic patients is not clearly understood. The aim of this study is to investigate the changes in sensitivity to cat and dog allergens in patients with respiratory allergies in Istanbul during the COVID-19 pandemic. Methods: Before the pandemic (March 2018 - March 2020) and during and after the pandemic (March 2020 - March 2022), a total of 5499 patients who underwent skin testing were retrospectively evaluated. The patients' age, gender, diagnosis, total IgE, and eosinophil values were recorded. Patients were divided into two groups: 2-6 years old and 7 years and older. The frequency of sensitization to cats and dogs was investigated in both groups before and after the pandemic. Results: The median age of the 5499 children included in the study was 77 months, with a range of 2 to 221 months. Furthermore, 55.7% of the children were male. Of the children, 59.1% were examined before the pandemic, and 40.9% during and after the pandemic. During the examinations, allergic rhinitis was identified in 1628 children (29.6%), asthma in 1829 children (33.3%), and both asthma and allergic rhinitis in 2042 children (37.1%). Allergies to cats were found in 247 children (4.5%), and to dogs in 166 children (3.0%). When comparing the age groups, the frequency of cat allergy in the 7-years and older group was found to have decreased compared to the pre-pandemic period, and the statistical difference was close to significance (p=0.08). However, regarding dog allergy, in the 7 years and older group, the sensitivity to dogs, which was 5.6% before the pandemic, had decreased to 2.6% during the pandemic, and this decrease was found to be statistically highly significant (p<0.001). Conclusion: Environmental allergen exposure has a significant impact on the phenotype of allergic diseases. Changes in patients' lifestyles and increased time spent at home during the pandemic may have led to a decrease in contact with outdoor cat and dog allergens, resulting in a reduced frequency of cat and dog sensitivity. Additionally, the introduction of mask-distance-handwashing/disinfection rules during the pandemic is believed to have reduced contact with cat and dog allergens, potentially contributing to a decrease in allergy frequency.

TAD hierarchy restricts poised LTR activation and loss of TAD hierarchy promotes LTR co-option in cancer.

Transposable elements (TEs) are abundant in the human genome, and they provide the sources for genetic and functional diversity. The regulation of TEs expression and their functional consequences in physiological conditions and cancer development remain to be fully elucidated. Previous studies suggested TEs are repressed by DNA methylation and chromatin modifications. The effect of 3D chromatin topology on TE regulation remains elusive. Here, by integrating transcriptome and 3D genome architecture studies, we showed that haploinsufficient loss of NIPBL selectively activates alternative promoters at the long terminal repeats (LTRs) of the TE subclasses. This activation occurs through the reorganization of topologically associating domain (TAD) hierarchical structures and recruitment of proximal enhancers. These observations indicate that TAD hierarchy restricts transcriptional activation of LTRs that already possess open chromatin features. In cancer, perturbation of the hierarchical chromatin topology can lead to co-option of LTRs as functional alternative promoters in a context-dependent manner and drive aberrant transcriptional activation of novel oncogenes and other divergent transcripts. These data uncovered a new layer of regulatory mechanism of TE expression beyond DNA and chromatin modification in human genome. They also posit the TAD hierarchy dysregulation as a novel mechanism for alternative promoter-mediated oncogene activation and transcriptional diversity in cancer, which may be exploited therapeutically.

Characterizing acetogenic metabolism using a genome-scale metabolic reconstruction of Clostridium ljungdahlii.

BACKGROUND: The metabolic capabilities of acetogens to ferment a wide range of sugars, to grow autotrophically on H2/CO2, and more importantly on synthesis gas (H2/CO/CO2) make them very attractive candidates as production hosts for biofuels and biocommodities. Acetogenic metabolism is considered one of the earliest modes of bacterial metabolism. A thorough understanding of various factors governing the metabolism, in particular energy conservation mechanisms, is critical for metabolic engineering of acetogens for targeted production of desired chemicals. RESULTS: Here, we present the genome-scale metabolic network of Clostridium ljungdahlii, the first such model for an acetogen. This genome-scale model (iHN637) consisting of 637 genes, 785 reactions, and 698 metabolites captures all the major central metabolic and biosynthetic pathways, in particular pathways involved in carbon fixation and energy conservation. A combination of metabolic modeling, with physiological and transcriptomic data provided insights into autotrophic metabolism as well as aided the characterization of a nitrate reduction pathway in C. ljungdahlii. Analysis of the iHN637 metabolic model revealed that flavin based electron bifurcation played a key role in energy conservation during autotrophic growth and helped identify genes for some of the critical steps in this mechanism. CONCLUSIONS: iHN637 represents a predictive model that recapitulates experimental data, and provides valuable insights into the metabolic response of C. ljungdahlii to genetic perturbations under various growth conditions. Thus, the model will be instrumental in guiding metabolic engineering of C. ljungdahlii for the industrial production of biocommodities and biofuels.

Increased skin reactions with hydroxychloroquine during breast radiotherapy.

With the advances in radiation technology, skin reaction due to postoperative radiotherapy (RT) in breast cancer patients is generally mild and tolerable. However, certain drugs may increase the radiation effect. In literature, only few cases of adverse reactions in the radiation field have been reported with the use of Chloroquine. This report describes the case of a 30-year-old young female who had enhanced skin reactions with hydroxychloroquine (HCQ) treatment during breast RT. HCQ should be used with caution in patients undergoing RT due to its potential radiosensitizer effect.