dataesr/scientific-paragraphs-categorization huggingface dataset:
The history of hospitalization was traced back to 1995. Most of the diagnostic codes used in this study have been validated in previous NHIRD studies  [32, 33]. Information on medications was extracted 3 months before and after the index date, and was extracted from the claims data of outpatient visits, or the refill prescriptions for chronic illness in the pharmacy using the Anatomical Therapeutic Chemical codes, or Taiwan NHI reimbursement codes. The ICD diagnostic codes used in this study are provided in the supplement (Supplemental Table  S1 ).
Outcomes The main outcome was the duration between the date of advanced CKD diagnosis and the date of receiving kidney transplantation. The secondary outcomes were adverse events after kidney transplantation, including all-cause mortality, infection-associated hospitalization or death, newly diagnosed malignancy, osteoporosis-related fracture, new-onset diabetes mellitus, allograft failure requiring maintenance dialysis, and major cardiac and cerebrovascular events (MACCE). The latter were composed of acute myocardial infarction, acute ischemic stroke, intracerebral hemorrhage, heart failure hospitalization, and cardiovascular death. Information of date, place, and causes of mortality were available in the Taiwan Death Registry database which were included in HWDC. Components of MACCE were detected using a principal discharge diagnosis.
Infection-related hospitalization, including sepsis, was detected using the principal or secondary discharge diagnoses. Osteoporosis-related fracture was identified on the basis of the principal diagnosis of a hospitalization or emergency visit. Newly diagnosed malignancy and allograft failure requiring maintenance dialysis were identified from the catastrophic illness certificate sub-database of the NHIRD. New-onset diabetes mellitus required at least two newly performed outpatient diagnoses with a prescription of oral hypoglycemic agents (including sulfonylurea, metformin, alpha-glucosidase inhibitors, thiazolidinediones, meglitinides, dipeptidyl peptidase-4 inhibitor, glucagon-like peptide 1 receptor agonist and sodiumglucose cotransporters inhibitor) or insulin.
Discussion The importance of supplemented low-protein diets has been recently underlined in the new KDOQI guidelines, principally for their advantage of allowing a longer follow-up in the pre-dialysis phase  [35]. High-quality diets with appropriate restriction of protein have been regarded as a crucial treatment in CKD population  [36]. However, to the best of our knowledge, only one small study had focused on the advantage of this policy while waiting for pancreas-kidney transplantation, and no study had been performed to analyze the effect of this dietary approach on delaying time to transplantation in patients scheduled for living-donor kidney transplantation  [21]. Our study was performed in Taiwan, employing the NHIRD, a comprehensive nationwide database; it suggests that sLPDs may safely delay the timing of preemptive kidney transplantation among patients with advanced CKD.
Therefore, even after using a nationwide database, the number of enrolled patients was limited in this study. Second, laboratory data, including serum albumin, creatinine, lipid profile, proteinuria, and hemoglobin, were not available in the NHIRD. In addition, the information on medical institutions and socioeconomic status of enrollees was not available in the dataset, and differences among these covariates may theoretically influence the results. Third, in an observational study, removing all potential confounders is impossible regardless of the study design, which may further bias the results. Namely, the possibility cannot be excluded that patients with a slower progression of CKD, or with better compliance, were selected. Fourth, this study was based on a Taiwanese database. Therefore, the results of the current study may not apply entirely to other populations because of cultural, dietary, and genetic differences.
Fourth, although this study suggests that the use of sLPDs may delay the need of preemptive kidney transplantation, and without increasing short-term adverse events, it was not clear if delaying access to the transplantation would result in longer life expectancy or better quality of life. Lastly, the details of the diets were not available in the database, and the characteristics of the donors could not be identified. Most of these limitations are linked to the study design; however, a randomized control study would be hardly feasible, as well as possibly unsound from an ethical point of view, since diets need commitment and compliance is crucial  [40, 41]. Accepting these limitations, in conclusion, this study suggests that sLPDs have the potential to delay the timing of preemptive kidney transplantation, without increasing the risk of post-transplantation adverse events.
Acknowledgments: We thank two biostatisticians,  Alfred Hsing-Fen Lin  and  Zoe Ya-Zhu Syu , for the consultation in the statistical analysis during the completion of the manuscript. This study was supported by grants from  Chang Gung Memorial Hospital, Taiwan  ( CORPG5G0081 ,  BMRPD97 ). C. -H. Chang was supported by the  Ministry of Science and Technology  ( 106-2314-B-182A-118-MY3 ).
quickly after complete removal of tumour cells. 4 ] [10]  Ji et al. 8  reported an increased risk of cancer with an overall standardized incidence ratio (SIR) of 1. 19 after hospitalization. Similarly, Muller et al. 9  reported an increased risk of malignancy in the first 6 months following a diagnosis of PMR [Hazard ratio: 1. 69 (95% CI 1. 18-2. 42)]. However, because these studies were conducted in hospitals, and/or in large retrospective institutional databases, there is a potential source of selection bias. In addition, neither study evaluated what investigations should be performed to rule out malignancy, while it is well known that many of the investigations used to detect primary cancer are not effective in patients with cancer of unknown origin. 11, 12  real-life practice, thoracic, pelvic, and abdominal CT-scan (CT-TAP) is the most widely used imaging tool for finding occult cancer when suspected, but its value in patients presenting symptoms of PMR is not known.
Univariate and multivariate analyses were then performed in order to evaluate the potential predictive factors for confirmed cancers that were diagnosed using the standardized evaluation. The variables of interest were age, gender, a history of cancer, disease duration, ESR and serum CRP levels. Proportions of categorical variables (gender and history of cancer) and means/medians of continuous variables (age, disease duration, ESR and CRP levels) were compared between patients with and without confirmed cancer using Fisher's exact test and analysis of variance/Kruskal-Wallis test, respectively. A p-value of <0. 05 was considered statistically significant. SAS 9. 3 (SAS Institute Inc. , Cary, North Carolina) was used for statistical analyses.
Results In total, 118 patients fulfilling 2012 ACR/ EULAR classification criteria for PMR were included: 68 women and 50 men, median age 73 years, median disease duration 10 weeks. Fifteen patients (13%) had cancer in their past medical history (four breast cancer, two each of prostate and non-melanoma skin cancer, and one each of kidney, kidney and prostate, tongue, cervical cancer, melanoma, lymphoma and myeloproliferative disorder). There were some missing data for PSA measurements (n = 9). The results of the standardized evaluation are shown in Table  1. PSA levels were elevated in eight (19%) men. Subsequent evaluations including prostate biopsy ruled out cancer in seven patients and were not performed in one patient. CT-TAP showed an abnormal mass or adenopathy in 33 patients. In these patients, subsequent testing led to the diagnosis of histologically confirmed cancer in nine patients (four kidney carcinoma, two lung cancer, one each of pancreatic, colon, and ampullary carcinoma) and of possible or probable cancer in two patients.
Nevertheless, no link was found between these conditions, with an odds ratio (OR) of 0. 81 (95% CI: 0. 67-0. 98). Using an American cancer registry, Anderson et al. 23   24  and Hodgkin lymphoma (SIR = 2. 2),  25  using data from a Swedish healthcare database. All of these studies were conducted from national registries and found that the lymphoma appeared generally within 1 year of the diagnosis of PMR. However, our study was not designed for screening non-Hodgkin or Hodgkin lymphoma. The present results might have important clinical implications. Indeed, the majority of studies have reported an increase in the incidence rate of cancer in the years after a diagnosis of PMR, and some of these studies implemented close follow-up that is not representative of real-life practice. Another major point is the corticosteroid resistance in case of paraneoplastic syndrome with PMR symptoms.
Population under study After The national Biomedical Ethics Committee of the Department of Health and Preventive Medicine of Dakar (Senegal) approved the epidemiological study, the participants were informed about the aim of this research. The subjects were asked to fill in a personal data questionnaire, including detailed information on their place of residence, duration of residence, occupational history, medical history (e. g. , kidney diseases), present status, etc. Persons with kidney diseases, diabetes or known occupational exposure to Cd and/or Pb as well as those living on the respective sites for less than 5 years were excluded from the study based on the questionnaire data. In total, 87 persons (i. e. , 52 exposed subjects and 35 control subjects) were enrolled in the study (Table  1 ).
Statistical analysis Group general characteristics, Pb and Cd exposure levels, and blood and urine biomarker levels were expressed as mean value ± standard deviation. Data analyses were performed using SPSS 25. 0 for Windows (SPSS, Paris, France). Comparisons were carried out between the control and the exposed subjects (Mann-Whitney U test). Thereafter, we looked for the blood or urinary renal injury biomarkers significantly associated with Pb and Cd exposure levels with single linear regression models (Pearson test).
Acknowledgements The research described in this article benefited from grants from the  "Centre de Recherche pour le Dévelopement International" (CRDI) of Dakar (Senegal). The "Ministère de l'Enseignement Supérieur et de la Recherche" of Dakar (Senegal)  " and the  Agence Universitaire de la Francophonie" (AUF)  provided  Mathilde Cabral 's mobility financial support. We are particularly grateful to  Dr Mbaye Diaw Dioum  for his useful suggestions and careful rereading of the article.
Dynamic Light Scattering (DLS) Dynamic light scattering measurements were made with a Zetasizer Ultra (Malvern Panalytical Ltd. , Malvern, UK) using a He-Ne laser at a wavelength of 633 nm and maximum power of 10 mW. Five repeat measurements of each sample were made, using backscatter detection and a low-volume quartz batch cuvette (ZEN2112 Malvern Panalytical Ltd. , Malvern. UK). The instrument settings were optimized automatically by means of the ZS XPLORER software (Malvern Panalytical Ltd. , Malvern, UK). Vaccines 2022, 10, 49 5 of 35.
Multi-Angle Dynamic Light Scattering (MADLS) Multiangle dynamic light scattering (MADLS) particle concentration measurements were carried out using a Zetasizer Ultra (Malvern Panalytical Ltd. , Malvern, UK) using a He-Ne laser at a wavelength of 633 nm and maximum power of 10 mW. All experiments were carried out at 25 • C unless stated otherwise. The instrument has a tolerance of 0. 1 • C. All measurements were carried out in a low-volume quartz batch cuvette (ZEN2112 Malvern Panalytical Ltd. , Malvern. UK). The instrument settings were optimized automatically by means of the ZS XPLORER software (Malvern Panalytical Ltd. , Malvern, UK). The particle optical properties used for the measurements were calculated assuming solid sphere and using the data from nucleoside analysis for determination of RNA content and lipid content, respectively  [10].
Electrophoretic Light Scattering (ELS) Electrophoretic light scattering (ELS) measurements of the lipid nanoparticles samples were measured on a Zetasizer Ultra Red instrument (Malvern Panalytical Ltd. , Malvern, UK) equipped with a He-Ne laser at a wavelength of 633 nm and maximum power of 10 mW. Amounts of 700 µL of the samples were introduced into a folded capillary cell (DTS1070 Malvern Panalytical Ltd. , Malvern, UK). The duration of the zeta potential measurements was manually set up with 10 sub runs used per measurement. All other measurement settings were optimized automatically by the ZS XPLORER software. All measurements were made at 25 • C and consisted of 3 zeta potential measurements followed by 5 DLS size measurements using backscatter detection. A 60 s delay between each zeta potential measurement was used to minimize Joule heating and polarization effects.
The samples were maintained at 4 • C in the autosampler prior to injection. The column oven and detector module were maintained at a constant 30 • C during this work. Compositional analysis method  [56]  was employed to determine the concentration and molecular weight of two distinct components within a sample. For the compositional analysis to work, it is necessary to know the refractive index increment (dn/dc) and extinction coefficient (dA/dc) of both components. In general, the vaccine is divided into the delivery vehicle and the genomic contents or API. For the example of rAAVs discussed below, the dn/dc values of the capsid and the ssDNA are well known. The dA/dc for the capsid is measured using OMNISEC, and the dA/dc for the ssDNA is calculated from the sequence. The values used for these components were: dn/dc capsid rAAV5 0.
The data were analyzed with dedicated PEAQ DSC Analysis software (Malvern Panalytical, Northampton, MA). For analysis, sample thermograms were normalized for the sample concentration and corrected for the instrument baseline by subtraction of the corresponding buffer-buffer scan. Finally, the sample thermograms were automatically baseline-corrected following extrapolation of pre-and post-transition baselines with a spline function. The resulting normalized and baseline-corrected DSC traces of rAAV5, mRNA-LNPs and free mRNA samples were analyzed for T onset , T m , total heat effect and enthalpy of transition, ∆H tr.
9 confirming it consists of 26. 1% genetic material. Applying the compositional analysis on the samples also produces results for the samples' CQAs. It shows the full rAAV5, rAAV9 and rAAV2 consist of 78, 77 and 80% filled monomer particles and have vp/vg ratios of 1. 29, 1. 30 and 1. 25, respectively (Table  4 ). Additionally, the particle concentration is produced and is labelled total AAV titer. Analyzing the monomer peak in each rAAV9 and rAAV2 nominally full and empty with the compositional analysis of the OMNISEC software, the percentage full, the vp/vg ratio and the particle titer are produced from a single measurement. The samples are simply differentiated by the software by applying the appropriate dn/dc and dA/dc values for the two components of each of the serotypes. Empty and full rAAVs of a given serotype were then mixed to give 3 additional points that when measured would indicate how accurately the % full rAAV could be measured over a range of percentage full particles.
A dip in the DSC signal can be observed on the thermogram of the full rAAV5 sample in the temperature range preceding the main peak. This deviating behavior is corroborated by the light scattering intensity data which also shows markedly different trends for the full and the empty rAAV5 samples in this temperature range (cf. inserts in Figure  11 ). In addition, a pre-transition shoulder at temperatures preceding the main transition is observed only on the DSC thermogram of the empty rAAV5 sample. The differences persist in the temperature range following the main peak, where an additional transition is detected for the full rAAV5 sample and centered around 94. 7 • C. This additional higher temperature transition is markedly different from the Tm value specific to the rAAV5 serotype and could be attributed to structural transitions of ssDNA molecules released upon disintegration of the rAAV5 capsids  [20].
The maximum value observed for the mean scattering intensity of the empty rAAV5 is significantly lower than the value observed for the full rAAV5. These trends are reproduced for diluted rAAV5 samples (data not shown). The overall changes in z-average size with temperature could contain a contribution from the changes in viscosity of the samples. However, as the same buffer was used for the two rAAV5 samples compared in these DLS thermal ramps, any changes in sample viscosity would originate from the changes in the state of the rAAV5 samples.
Unrestricted Document tering intensity and z-average size (cf. inserts Figure  12 ). The difference in the response of the two rAAV5 samples to thermal stress becomes even more pronounced at temperature range >85 °C. This temperature range is accompanied by a fast increase of the mean scattering intensity and z-average size for the full rAAV5 sample, and a gradual increase of the mean scattering intensity and z-average size followed by a downturn for the empty rAAV5. The maximum value observed for the mean scattering intensity of the empty rAAV5 is significantly lower than the value observed for the full rAAV5. These trends are reproduced for diluted rAAV5 samples (data not shown). The overall changes in z-average size with temperature could contain a contribution from the changes in viscosity of the samples.
MADLS provides improved resolution compared to DLS, but not as high as NTA, as seen in the mRNA-LNP1 data where NTA can identify secondary populations present in the sample. In the MVA sample, NTA is also capable of showing the increased resolution in the size distribution  [57]. For a deeper insight into the size distribution, higher resolution methods using a separation method, such as SEC or FFF, can improve the understanding of the full population present in the sample, as demonstrated in the two batches of rAAV5 samples (Figure  3  and Tables  5  and 6 ). Here, it is clear how MADLS is a very sensitive screening tool for the presence of small amounts of larger material. However, it cannot resolve close populations such as monomers and small oligomers, but it requires a separation technique such as SEC-SLS to detect and quantify small oligomers.
Importantly, for robust measurements, it should be verified that the particle system is stable upon any required dilution, often done simply by measuring the particle size distribution repeatedly over time and monitoring the sample for any trends. SEC-SLS can measure concentrations of particles that are capable of being separated on a SEC column, so typically smaller than 200 nm in diameter. The OMNISEC SEC system uses information from multiple detectors to produce various results with the particle concentration results determined from data obtained with the light scattering detector and differential refractometer. The limitation of the results is therefore dependent on the two detectors. The signal observed from the RI detector is dependent on the concentration of the sample, and the light scattering detector signal is dependent on the molecular weight and concentration.
DSC traces, along with the corresponding values of total heat effect, enthalpy of transitions, ∆H tr , the midpoint temperature of a thermal transition, T m and the temperature of the onset of thermal transition, T onset , serve as sample-specific fingerprints enabling detailed characterization and comparison of thermal stability and Higher Oder Structure of biomolecules in solutions. DLS thermal ramp data report changes in the mean light scattering intensity of a samples as a function of temperature. It also provides information on the size and the polydispersity of a sample in solution at each temperature point in a sequence of DLS measurements collected during the thermal ramp. A change in the light scattering intensity of a sample can arise from a change in sample concentration, sample size and homogeneity as well as a shift in the refractive index of the sample and/or dispersant caused by change of temperature.
T m values are generally quite similar for empty and full AAV capsids of one serotype, and they have no clear correlation with capsid dynamics, capsid uncoating, and genome release. New biophysical approaches are required to inform on the stability of AAV vectors to support their design and formulation development. The thermal stability of empty and full rAAV5 samples evaluated by DSC, and the parameters of the thermal transitions detected for the two samples, have been previously reported  [20]. In this study, the details of the observed thermal transitions by combining the DSC results with the trends in particle size and light scattering intensity obtained from DLS thermal ramps conducted on the empty and the full rAAV5 samples have been explored. The combination of these orthogonal techniques, and the published data on the thermal stability of AAV vectors collected with atomic force microscopy, transmission electron microscopy, biochemical assay and fluorimetric detection  [70, 71] , enabled more detailed mapping of structural changes occurring in the rAAV5 samples during temperature stress.
However, a better understanding of their complex structure and behavior in solution is required to control production and to secure designed function and stability on storage. DSC is a well-established technique to monitor phase transitions of lipids  [72] , structural transitions of nucleic acids, their complexes with cationic lipids  [48, [73] [74] [75] [76]  and thermal stability of lipid-based delivery vectors,  [12, 55]. In this study, DSC has been used to explore thermally induced structural transitions of the free mRNA and the mRNA-lipid complexes in mRNA-LNP1 and mRNA-LNP2 samples. Sample complexity makes detailed analysis and data interpretation challenging, and a combination of DSC with DLS size and thermal ramp measurements to increase the level of insight and reliability of the data interpretation have been used.
Apart from similar Tm values (cf. 89. 43 and 89. 68 • C) characteristic of the rAAV5 serotype [38, 64]  and the similar ∆H tr values for the main transitions (cf. 2360 and 2260 kJ/ (mole VP protein)), the empty and full rAAV5 samples show different responses to thermal stress according to the DSC data. A dip in the DSC signal can be observed on the thermogram of the full rAAV5 sample in the temperature range preceding the main peak. This deviating behavior is corroborated by the light scattering intensity data which also shows markedly different trends for the full and the empty rAAV5 samples in this temperature range (cf. inserts in Figure11). In addition, a pre-transition shoulder at temperatures preceding the main transition is observed only on the DSC thermogram of the empty rAAV5 sample.
inserts Figure12). The difference in the response of the two rAAV5 samples to thermal stress becomes even more pronounced at temperature range >85 • C. This temperature range is accompanied by a fast increase of the mean scattering intensity and z-average size for the full rAAV5 sample, and a gradual increase of the mean scattering intensity and z-average size followed by a downturn for the empty rAAV5. The maximum value observed for the mean scattering intensity of the empty rAAV5 is significantly lower than the value observed for the full rAAV5. These trends are reproduced for diluted rAAV5 samples (data not shown). The overall changes in z-average.